Redox Regulation of the Microcirculation

Cardiovascular Physiology > Microcirculation > Regulation of the Microvascular Blood Flow

Email a friend
Contact the editor about this article
How to cite

Andrew O. Kadlec, David D. Gutterman

10.1002/cphy.c180039

Source: Volume 10, Issue 1, January 2020

Published online: December 2019

Full Article on Wiley Online Library

Abstract
Images
References

Abstract

The microcirculation maintains tissue homeostasis through local regulation of blood flow and oxygen delivery. Perturbations in microvascular function are characteristic of several diseases and may be early indicators of pathological changes in the cardiovascular system and in parenchymal tissue function. These changes are often mediated by various reactive oxygen species and linked to disruptions in pathways such as vasodilation or angiogenesis. This overview compiles recent advances relating to redox regulation of the microcirculation by adopting both cellular and functional perspectives. Findings from a variety of vascular beds and models are integrated to describe common effects of different reactive species on microvascular function. Gaps in understanding and areas for further research are outlined. © 2020 American Physiological Society. Compr Physiol 10:229‐260, 2020.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

	Figure 1. Subcellular localization of vascular ROS generation.
	Figure 2. Oxidation and reduction of protein cysteine residues by hydrogen peroxide. Reproduced, with permission, from Burgoyne JR, et al., 2013 54.
	Figure 3. ROS detoxification by glutathione and peroxiredoxin/thioredoxin pathways. Reproduced, with permission, from Bindoli A, et al., 2008 33.
	Figure 4. Hydrogen peroxide signaling pathways that mediate vasodilation 53,55,58,110,139,256,266,310,338,349,376.
	Figure 5. Triphasic effect of H₂O₂ on the vasculature. At low concentrations, H₂O₂ promotes vascular homeostasis, but very low or high concentrations promote vascular inflammation and impaired function.

Figure 1. Subcellular localization of vascular ROS generation.

Figure 2. Oxidation and reduction of protein cysteine residues by hydrogen peroxide. Reproduced, with permission, from Burgoyne JR, et al., 2013 54.

Figure 3. ROS detoxification by glutathione and peroxiredoxin/thioredoxin pathways. Reproduced, with permission, from Bindoli A, et al., 2008 33.

Figure 4. Hydrogen peroxide signaling pathways that mediate vasodilation 53,55,58,110,139,256,266,310,338,349,376.

Figure 5. Triphasic effect of H₂O₂ on the vasculature. At low concentrations, H₂O₂ promotes vascular homeostasis, but very low or high concentrations promote vascular inflammation and impaired function.

References
1.	Adachi T, Matsui R, Xu S, Kirber M, Lazar HL, Sharov VS, Schoneich C, Cohen RA. Antioxidant improves smooth muscle sarco/endoplasmic reticulum Ca(2+)‐ATPase function and lowers tyrosine nitration in hypercholesterolemia and improves nitric oxide‐induced relaxation. Circ Res 90: 1114‐1121, 2002.
2.	Adili R, Tourdot BE, Mast K, Yeung J, Freedman JC, Green A, Luci DK, Jadhav A, Simeonov A, Maloney DJ, Holman TR, Holinstat M. First selective 12‐LOX inhibitor, ML355, impairs thrombus formation and vessel occlusion in vivo with minimal effects on hemostasis. Arterioscler Thromb Vasc Biol 37 (10): 1828‐1839, 2017.
3.	Ait‐Aissa K, Ebben JD, Kadlec AO, Beyer AM. Friend or foe? Telomerase as a pharmacological target in cancer and cardiovascular disease. Pharmacol Res 111: 422‐433, 2016.
4.	Akiyama E, Sugiyama S, Matsuzawa Y, Konishi M, Suzuki H, Nozaki T, Ohba K, Matsubara J, Maeda H, Horibata Y, Sakamoto K, Sugamura K, Yamamuro M, Sumida H, Kaikita K, Iwashita S, Matsui K, Kimura K, Umemura S, Ogawa H. Incremental prognostic significance of peripheral endothelial dysfunction in patients with heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol 60: 1778‐1786, 2012.
5.	Aley PK, Porter KE, Boyle JP, Kemp PJ, Peers C. Hypoxic modulation of Ca2+ signaling in human venous endothelial cells. Multiple roles for reactive oxygen species. J Biol Chem 280: 13349‐13354, 2005.
6.	Ali MH, Pearlstein DP, Mathieu CE, Schumacker PT. Mitochondrial requirement for endothelial responses to cyclic strain: Implications for mechanotransduction. Am J Physiol Lung Cell Mol Physiol 287: L486‐L496, 2004.
7.	Ali MH, Schumacker PT. Endothelial responses to mechanical stress: Where is the mechanosensor? Crit Care Med 30: S198‐S206, 2002.
8.	Amaral SL, Zorn TM, Michelini LC. Exercise training normalizes wall‐to‐lumen ratio of the gracilis muscle arterioles and reduces pressure in spontaneously hypertensive rats. J Hypertens 18: 1563‐1572, 2000.
9.	Ammar RF Jr, Gutterman DD, Brooks LA, Dellsperger KC. Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes. Cardiovasc Res 47: 595‐601, 2000.
10.	Ammar RF Jr, Gutterman DD, Brooks LA, Dellsperger KC. Impaired dilation of coronary arterioles during increases in myocardial O(2) consumption with hyperglycemia. Am J Physiol Endocrinol Metab 279: E868‐E874, 2000.
11.	Amon M, Menger MD, Vollmar B. Heme oxygenase and nitric oxide synthase mediate cooling‐associated protection against TNF‐alpha‐induced microcirculatory dysfunction and apoptotic cell death. FASEB J 17: 175‐185, 2003.
12.	Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso‐Cartier L, Molango S, Heitz F, Merlot C, Szyndralewiez C, Page P, Brenner DA. Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56: 2316‐2327, 2012.
13.	Archer SL, Wu XC, Thebaud B, Moudgil R, Hashimoto K, Michelakis ED. O2 sensing in the human ductus arteriosus: Redox‐sensitive K+ channels are regulated by mitochondria‐derived hydrogen peroxide. Biol Chem 385: 205‐216, 2004.
14.	Baas AS, Berk BC. Differential activation of mitogen‐activated protein kinases by H2O2 and O2‐ in vascular smooth muscle cells. Circ Res 77: 29‐36, 1995.
15.	Bagi Z, Erdei N, Koller A. High intraluminal pressure via H2O2 upregulates arteriolar constrictions to angiotensin II by increasing the functional availability of AT1 receptors. Am J Physiol Heart Circ Physiol 295: H835‐H841, 2008.
16.	Bagi Z, Feher A, Cassuto J. Microvascular responsiveness in obesity: Implications for therapeutic intervention. Br J Pharmacol 165: 544‐560, 2012.
17.	Bagi Z, Ungvari Z, Koller A. Xanthine oxidase‐derived reactive oxygen species convert flow‐induced arteriolar dilation to constriction in hyperhomocysteinemia: Possible role of peroxynitrite. Arterioscler Thromb Vasc Biol 22: 28‐33, 2002.
18.	Baldus S, Koster R, Chumley P, Heitzer T, Rudolph V, Ostad MA, Warnholtz A, Staude HJ, Thuneke F, Koss K, Berger J, Meinertz T, Freeman BA, Munzel T. Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease. Free Radic Biol Med 39: 1184‐1190, 2005.
19.	Balmain S, Padmanabhan N, Ferrell WR, Morton JJ, McMurray JJ. Differences in arterial compliance, microvascular function and venous capacitance between patients with heart failure and either preserved or reduced left ventricular systolic function. Eur J Heart Fail 9: 865‐871, 2007.
20.	Baradaran A, Nasri H, Rafieian‐Kopaei M. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J Res Med Sci 19: 358‐367, 2014.
21.	Barua RS, Ambrose JA, Srivastava S, DeVoe MC, Eales‐Reynolds LJ. Reactive oxygen species are involved in smoking‐induced dysfunction of nitric oxide biosynthesis and upregulation of endothelial nitric oxide synthase: An in vitro demonstration in human coronary artery endothelial cells. Circulation 107: 2342‐2347, 2003.
22.	Bayraktutan U, Draper N, Lang D, Shah AM. Expression of functional neutrophil‐type NADPH oxidase in cultured rat coronary microvascular endothelial cells. Cardiovasc Res 38: 256‐262, 1998.
23.	Beauchamp MH, Sennlaub F, Speranza G, Gobeil F Jr, Checchin D, Kermorvant‐Duchemin E, Abran D, Hardy P, Lachapelle P, Varma DR, Chemtob S. Redox‐dependent effects of nitric oxide on microvascular integrity in oxygen‐induced retinopathy. Free Radic Biol Med 37: 1885‐1894, 2004.
24.	Beltran B, Mathur A, Duchen MR, Erusalimsky JD, Moncada S. The effect of nitric oxide on cell respiration: A key to understanding its role in cell survival or death. Proc Natl Acad Sci U S A 97: 14602‐14607, 2000.
25.	Benest AV, Stone OA, Miller WH, Glover CP, Uney JB, Baker AH, Harper SJ, Bates DO. Arteriolar genesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature. Arterioscler Thromb Vasc Biol 28: 1462‐1468, 2008.
26.	Berne RM. The role of adenosine in the regulation of coronary blood flow. Circ Res 47: 807‐813, 1980.
27.	Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: Molecular mechanisms and pathophysiological implications. J Physiol 555: 589‐606, 2004.
28.	Beyer AM, Durand MJ, Hockenberry J, Gamblin TC, Phillips SA, Gutterman DD. An acute rise in intraluminal pressure shifts the mediator of flow‐mediated dilation from nitric oxide to hydrogen peroxide in human arterioles. Am J Phys Heart Circ Phys 307: H1587‐H1593, 2014.
29.	Beyer AM, Freed JK, Durand MJ, Riedel M, Ait‐Aissa K, Green P, Hockenberry JC, Morgan RG, Donato AJ, Peleg R, Gasparri M, Rokkas CK, Santos JH, Priel E, Gutterman DD. Critical role for telomerase in the mechanism of flow‐mediated dilation in the human microcirculation. Circ Res 118: 856‐866, 2016.
30.	Beyer AM, Gutterman DD. Regulation of the human coronary microcirculation. J Mol Cell Cardiol 52: 814‐821, 2012.
31.	Beyer AM, Zinkevich N, Miller B, Liu Y, Wittenburg AL, Mitchell M, Galdieri R, Sorokin A, Gutterman DD. Transition in the mechanism of flow‐mediated dilation with aging and development of coronary artery disease. Basic Res Cardiol 112: 5, 2017.
32.	Bidani AK, Polichnowski AJ, Loutzenhiser R, Griffin KA. Renal microvascular dysfunction, hypertension and CKD progression. Curr Opin Nephrol Hypertens 22: 1‐9, 2013.
33.	Bindoli A, Fukuto JM, Forman HJ. Thiol chemistry in peroxidase catalysis and redox signaling. Antioxid Redox Signal 10: 1549‐1564, 2008.
34.	Bleeke T, Zhang H, Madamanchi N, Patterson C, Faber JE. Catecholamine‐induced vascular wall growth is dependent on generation of reactive oxygen species. Circ Res 94: 37‐45, 2004.
35.	Bohlen HG, Zhou X, Unthank JL, Miller SJ, Bills R. Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation. Am J Physiol Heart Circ Physiol 297: H1337‐H1346, 2009.
36.	Borniquel S, Valle I, Cadenas S, Lamas S, Monsalve M. Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC‐1alpha. FASEB J 20: 1889‐1891, 2006.
37.	Brauner EV, Forchhammer L, Moller P, Barregard L, Gunnarsen L, Afshari A, Wahlin P, Glasius M, Dragsted LO, Basu S, Raaschou‐Nielsen O, Loft S. Indoor particles affect vascular function in the aged: An air filtration‐based intervention study. Am J Respir Crit Care Med 177: 419‐425, 2008.
38.	Breton‐Romero R, Acin‐Perez R, Rodriguez‐Pascual F, Martinez‐Molledo M, Brandes RP, Rial E, Enriquez JA, Lamas S. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta 1843: 2403‐2413, 2014.
39.	Breton‐Romero R, Lamas S. Hydrogen peroxide signaling mediator in the activation of p38 MAPK in vascular endothelial cells. Methods Enzymol 528: 49‐59, 2013.
40.	Breton‐Romero R, Lamas S. Hydrogen peroxide signaling in vascular endothelial cells. Redox Biol 2: 529‐534, 2014.
41.	Britten MB, Zeiher AM, Schachinger V. Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long‐term outcome. Coron Artery Dis 15: 259‐264, 2004.
42.	Broeders MA, Tangelder GJ, Slaaf DW, Reneman RS, oude Egbrink MG. Endogenous nitric oxide protects against thromboembolism in venules but not in arterioles. Arterioscler Thromb Vasc Biol 18: 139‐145, 1998.
43.	Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez‐Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC Jr, Whitsel L, Kaufman JD, American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 121: 2331‐2378, 2010.
44.	Brookes PS, Kraus DW, Shiva S, Doeller JE, Barone MC, Patel RP, Lancaster JR Jr, Darley‐Usmar V. Control of mitochondrial respiration by NO*, effects of low oxygen and respiratory state. J Biol Chem 278: 31603‐31609, 2003.
45.	Brooks SE, Gu X, Samuel S, Marcus DM, Bartoli M, Huang PL, Caldwell RB. Reduced severity of oxygen‐induced retinopathy in eNOS‐deficient mice. Invest Ophthalmol Vis Sci 42: 222‐228, 2001.
46.	Brown GC, Cooper CE. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356: 295‐298, 1994.
47.	Bruch‐Gerharz D, Ruzicka T, Kolb‐Bachofen V. Nitric oxide in human skin: Current status and future prospects. J Invest Dermatol 110: 1‐7, 1998.
48.	Brueckl C, Kaestle S, Kerem A, Habazettl H, Krombach F, Kuppe H, Kuebler WM. Hyperoxia‐induced reactive oxygen species formation in pulmonary capillary endothelial cells in situ. Am J Respir Cell Mol Biol 34: 453‐463, 2006.
49.	Brunt KR, Fenrich KK, Kiani G, Tse MY, Pang SC, Ward CA, Melo LG. Protection of human vascular smooth muscle cells from H2O2‐induced apoptosis through functional codependence between HO‐1 and AKT. Arterioscler Thromb Vasc Biol 26: 2027‐2034, 2006.
50.	Buerk DG, Barbee KA, Jaron D. Nitric oxide signaling in the microcirculation. Crit Rev Biomed Eng 39: 397‐433, 2011.
51.	Burger D, Montezano AC, Nishigaki N, He Y, Carter A, Touyz RM. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/Rho kinase pathways targeted to lipid rafts. Arterioscler Thromb Vasc Biol 31: 1898‐1907, 2011.
52.	Burger D, Turner M, Munkonda MN, Touyz RM. Endothelial microparticle‐derived reactive oxygen species: Role in endothelial signaling and vascular function. Oxidative Med Cell Longev 2016: 5047954, 2016.
53.	Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, Eaton P. Cysteine redox sensor in PKGIa enables oxidant‐induced activation. Science 317: 1393‐1397, 2007.
54.	Burgoyne JR, Oka S, Ale‐Agha N, Eaton P. Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system. Antioxid Redox Signal 18: 1042‐1052, 2013.
55.	Burke‐Wolin T, Abate CJ, Wolin MS, Gurtner GH. Hydrogen peroxide‐induced pulmonary vasodilation: Role of guanosine 3',5'‐cyclic monophosphate. Am J Physiol 261: L393‐L398, 1991.
56.	Cabrales P, Tsai AG, Frangos JA, Intaglietta M. Role of endothelial nitric oxide in microvascular oxygen delivery and consumption. Free Radic Biol Med 39: 1229‐1237, 2005.
57.	Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 87: 840‐844, 2000.
58.	Cai H, Li Z, Davis ME, Kanner W, Harrison DG, Dudley SC Jr. Akt‐dependent phosphorylation of serine 1179 and mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase 1/2 cooperatively mediate activation of the endothelial nitric‐oxide synthase by hydrogen peroxide. Mol Pharmacol 63: 325‐331, 2003.
59.	Caja S, Enriquez JA. Mitochondria in endothelial cells: Sensors and integrators of environmental cues. Redox Biol 12: 821‐827, 2017.
60.	Canty JM, Iyer VS. Hydrogen peroxide and metabolic coronary flow regulation. J Am Coll Cardiol 50: 1279‐1281, 2007.
61.	Carlson BE, Arciero JC, Secomb TW. Theoretical model of blood flow autoregulation: Roles of myogenic, shear‐dependent, and metabolic responses. Am J Physiol Heart Circ Physiol 295: H1572‐H1579, 2008.
62.	Carlstrom M, Lai EY, Ma Z, Steege A, Patzak A, Eriksson UJ, Lundberg JO, Wilcox CS, Persson AE. Superoxide dismutase 1 limits renal microvascular remodeling and attenuates arteriole and blood pressure responses to angiotensin II via modulation of nitric oxide bioavailability. Hypertension 56: 907‐913, 2010.
63.	Cascino T, Csanyi G, Al Ghouleh I, Montezano AC, Touyz RM, Haurani MJ, Pagano PJ. Adventitia‐derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen‐activated protein kinase. Antioxid Redox Signal 15: 1507‐1515, 2011.
64.	Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS. Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39: 269‐274, 2002.
65.	Chan EL, Murphy JT. Reactive oxygen species mediate endotoxin‐induced human dermal endothelial NF‐kappaB activation. J Surg Res 111: 120‐126, 2003.
66.	Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia‐inducible factor‐1α during hypoxia: A mechanism of O2 sensing. J Biol Chem 275: 25130‐25138, 2000.
67.	Chatzianagnostou K, Del Turco S, Pingitore A, Sabatino L, Vassalle C. The mediterranean lifestyle as a non‐pharmacological and natural antioxidant for healthy aging. Antioxidants (Basel) 4: 719‐736, 2015.
68.	Chawengsub Y, Gauthier KM, Campbell WB. Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 297: H495‐H507, 2009.
69.	Chen JX, Zeng H, Lawrence ML, Blackwell TS, Meyrick B. Angiopoietin‐1‐induced angiogenesis is modulated by endothelial NADPH oxidase. Am J Physiol Heart Circ Physiol 291: H1563‐H1572, 2006.
70.	Chen K, Keaney JF Jr. Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease. Curr Atheroscler Rep 14: 476‐483, 2012.
71.	Chen X, Andresen BT, Hill M, Zhang J, Booth F, Zhang C. Role of reactive oxygen species in tumor necrosis factor‐alpha induced endothelial dysfunction. Curr Hypertens Rev 4: 245‐255, 2008.
72.	Cheng TH, Shih NL, Chen CH, Lin H, Liu JC, Chao HH, Liou JY, Chen YL, Tsai HW, Chen YS, Cheng CF, Chen JJ. Role of mitogen‐activated protein kinase pathway in reactive oxygen species‐mediated endothelin‐1‐induced beta‐myosin heavy chain gene expression and cardiomyocyte hypertrophy. J Biomed Sci 12: 123‐133, 2005.
73.	Chrissobolis S, Didion SP, Kinzenbaw DA, Schrader LI, Dayal S, Lentz SR, Faraci FM. Glutathione peroxidase‐1 plays a major role in protecting against angiotensin II‐induced vascular dysfunction. Hypertension 51: 872‐877, 2008.
74.	Chua CC, Hamdy RC, Chua BH. Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells. Free Radic Biol Med 25: 891‐897, 1998.
75.	Cifuentes‐Pagano E, Meijles DN, Pagano PJ. The quest for selective nox inhibitors and therapeutics: Challenges, triumphs and pitfalls. Antioxid Redox Signal 20: 2741‐2754, 2014.
76.	Cifuentes‐Pagano E, Saha J, Csanyi G, Ghouleh IA, Sahoo S, Rodriguez A, Wipf P, Pagano PJ, Skoda EM. Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors. Medchemcomm 4: 1085‐1092, 2013.
77.	Clempus RE, Griendling KK. Reactive oxygen species signaling in vascular smooth muscle cells. Cardiovasc Res 71: 216‐225, 2006.
78.	Clifford PS. Local control of blood flow. Adv Physiol Educ 35: 5‐15, 2011.
79.	Connor KM, Subbaram S, Regan KJ, Nelson KK, Mazurkiewicz JE, Bartholomew PJ, Aplin AE, Tai YT, Aguirre‐Ghiso J, Flores SC, Melendez JA. Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J Biol Chem 280: 16916‐16924, 2005.
80.	Cooper A, Heagerty AM. Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia. Am J Phys 275: H1482‐H1488, 1998.
81.	Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor‐alpha is mediated by ceramide. Am J Respir Cell Mol Biol 24: 762‐768, 2001.
82.	Cornelissen AJ, Dankelman J, VanBavel E, Spaan JA. Balance between myogenic, flow‐dependent, and metabolic flow control in coronary arterial tree: A model study. Am J Physiol Heart Circ Physiol 282: H2224‐H2237, 2002.
83.	Creager MA, Cooke JP, Mendelsohn ME, Gallagher SJ, Coleman SM, Loscalzo J, Dzau VJ. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest 86: 228‐234, 1990.
84.	Csanyi G, Cifuentes‐Pagano E, Al Ghouleh I, Ranayhossaini DJ, Egana L, Lopes LR, Jackson HM, Kelley EE, Pagano PJ. Nox2 B‐loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2. Free Radic Biol Med 51: 1116‐1125, 2011.
85.	Csanyi G, Taylor WR, Pagano PJ. NOX and inflammation in the vascular adventitia. Free Radic Biol Med 47: 1254‐1266, 2009.
86.	Csiszar A, Ungvari Z, Edwards JG, Kaminski P, Wolin MS, Koller A, Kaley G. Aging‐induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 90: 1159‐1166, 2002.
87.	Cudkowicz ME, McKenna‐Yasek D, Chen C, Hedley‐Whyte ET, Brown RH Jr. Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene. Ann Neurol 43: 703‐710, 1998.
88.	Dai DF, Hsieh EJ, Chen T, Menendez LG, Basisty NB, Tsai L, Beyer RP, Crispin DA, Shulman NJ, Szeto HH, Tian R, MacCoss MJ, Rabinovitch PS. Global proteomics and pathway analysis of pressure‐overload‐induced heart failure and its attenuation by mitochondrial‐targeted peptides. Circ Heart Fail 6: 1067‐1076, 2013.
89.	Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves‐Cintron M, Chen T, Marcinek DJ, Dorn GW 2nd, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS. Mitochondrial oxidative stress mediates angiotensin II‐induced cardiac hypertrophy and Galphaq overexpression‐induced heart failure. Circ Res 108: 837‐846, 2011.
90.	Dai G, Kaazempur‐Mofrad MR, Natarajan S, Zhang Y, Vaughn S, Blackman BR, Kamm RD, Garcia‐Cardena G, Gimbrone MA Jr. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis‐susceptible and ‐resistant regions of human vasculature. Proc Natl Acad Sci U S A 101: 14871‐14876, 2004.
91.	Daiber A, Di Lisa F, Oelze M, Kroller‐Schon S, Steven S, Schulz E, Munzel T. Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function. Br J Pharmacol, 2015.
92.	D'Angelo G, Loria AS, Pollock DM, Pollock JS. Endothelin activation of reactive oxygen species mediates stress‐induced pressor response in Dahl salt‐sensitive prehypertensive rats. Hypertension 56: 282‐289, 2010.
93.	Datla SR, Peshavariya H, Dusting GJ, Mahadev K, Goldstein BJ, Jiang F. Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro. Arterioscler Thromb Vasc Biol 27: 2319‐2324, 2007.
94.	Davenpeck KL, Gauthier TW, Lefer AM. Inhibition of endothelial‐derived nitric oxide promotes P‐selectin expression and actions in the rat microcirculation. Gastroenterology 107: 1050‐1058, 1994.
95.	de Jongh RT, Serne EH, IJzerman RG, de Vries G, Stehouwer CD. Impaired microvascular function in obesity: Implications for obesity‐associated microangiopathy, hypertension, and insulin resistance. Circulation 109: 2529‐2535, 2004.
96.	De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK. Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: Role of a superoxide‐producing NADH oxidase. Circ Res 82: 1094‐1101, 1998.
97.	de Wit C, Roos F, Bolz SS, Pohl U. Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion. Physiol Genomics 13: 169‐177, 2003.
98.	DeLano FA, Parks DA, Ruedi JM, Babior BM, Schmid‐Schonbein GW. Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously hypertensive rat. Microcirculation 13: 551‐566, 2006.
99.	DelloStritto DJ, Connell PJ, Dick GM, Fancher IS, Klarich B, Fahmy JN, Kang PT, Chen YR, Damron DS, Thodeti CK, Bratz IN. Differential regulation of TRPV1 channels by H2O2: Implications for diabetic microvascular dysfunction. Basic Res Cardiol 111: 21, 2016.
100.	Di Marco E, Gray SP, Kennedy K, Szyndralewiez C, Lyle AN, Lassegue B, Griendling KK, Cooper ME, Schmidt HH, Jandeleit‐Dahm KA. NOX4‐derived reactive oxygen species limit fibrosis and inhibit proliferation of vascular smooth muscle cells in diabetic atherosclerosis. Free Radic Biol Med 97: 556‐567, 2016.
101.	Dickinson BC, Chang CJ. A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells. J Am Chem Soc 130: 9638‐9639, 2008.
102.	Diederich D, Skopec J, Diederich A, Dai FX. Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: Role of free radicals. Am J Phys 266: H1153‐H1161, 1994.
103.	Dignat‐George F, Boulanger CM. The many faces of endothelial microparticles. Arterioscler Thromb Vasc Biol 31: 27‐33, 2011.
104.	Dikalov SI, Harrison DG. Methods for detection of mitochondrial and cellular reactive oxygen species. Antioxid Redox Signal 20: 372‐382, 2014.
105.	Dikalov SI, Ungvari Z. Role of mitochondrial oxidative stress in hypertension. Am J Physiol Heart Circ Physiol 305: H1417‐H1427, 2013.
106.	Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, Harrison DG, Dikalov SI. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 107: 106‐116, 2010.
107.	Dimitropoulou C, Han G, Miller AW, Molero M, Fuchs LC, White RE, Carrier GO. Potassium (BK(Ca)) currents are reduced in microvascular smooth muscle cells from insulin‐resistant rats. Am J Physiol Heart Circ Physiol 282: H908‐H917, 2002.
108.	Ding H, Aljofan M, Triggle CR. Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells. J Cell Physiol 212: 682‐689, 2007.
109.	Ding Z, Godecke A, Schrader J. Contribution of cytochrome P450 metabolites to bradykinin‐induced vasodilation in endothelial NO synthase deficient mouse hearts. Br J Pharmacol 135: 631‐638, 2002.
110.	Dong DL, Yue P, Yang BF, Wang WH. Hydrogen peroxide stimulates the Ca(2+)‐activated big‐conductance K channels (BK) through cGMP signaling pathway in cultured human endothelial cells. Cell Physiol Biochem 22: 119‐126, 2008.
111.	Dong L, Zheng YM, Van Riper D, Rathore R, Liu QH, Singer HA, Wang YX. Functional and molecular evidence for impairment of calcium‐activated potassium channels in type‐1 diabetic cerebral artery smooth muscle cells. J Cereb Blood Flow Metab 28: 377‐386, 2008.
112.	Dora KA, Doyle MP, Duling BR. Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles. Proc Natl Acad Sci U S A 94: 6529‐6534, 1997.
113.	Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 82: 47‐95, 2002.
114.	Duffy SJ, Castle SF, Harper RW, Meredith IT. Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow‐mediated dilation in human coronary circulation. Circulation 100: 1951‐1957, 1999.
115.	Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev 88: 1009‐1086, 2008.
116.	Duncker DJ, Stubenitsky R, Verdouw PD. Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise. Am J Phys 275: H1663‐H1672, 1998.
117.	Durán WN, Sánchez FA, Breslin JW. Microcirculatory exchange function. In: Microcirculation. Academic Press, 2008, p. 81‐124.
118.	Durand MJ, Dharmashankar K, Bian JT, Das E, Vidovich M, Gutterman DD, Phillips SA. Acute exertion elicits a H2O2‐dependent vasodilator mechanism in the microvasculature of exercise‐trained but not sedentary adults. Hypertension 65: 140‐145, 2015.
119.	Durand MJ, Gutterman DD. Diversity in mechanisms of endothelium‐dependent vasodilation in health and disease. Microcirculation 20: 239‐247, 2013.
120.	Eiserich JP, Baldus S, Brennan M‐L, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA. Myeloperoxidase, a Leukocyte‐Derived Vascular NO Oxidase. Science 296: 2391‐2394, 2002.
121.	Endlich N, Endlich K, Taesch N, Helwig JJ. Culture of vascular smooth muscle cells from small arteries of the rat kidney. Kidney Int 57: 2468‐2475, 2000.
122.	Erdei N, Toth A, Pasztor ET, Papp Z, Edes I, Koller A, Bagi Z. High‐fat diet‐induced reduction in nitric oxide‐dependent arteriolar dilation in rats: Role of xanthine oxidase‐derived superoxide anion. Am J Physiol Heart Circ Physiol 291: H2107‐H2115, 2006.
123.	Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, Zaharris E, Gupta M, Clearfield M, Libby P, Hasan AA, Glynn RJ, Ridker PM. Rationale and design of the Cardiovascular Inflammation Reduction Trial: A test of the inflammatory hypothesis of atherothrombosis. Am Heart J 166: 199‐207.e115, 2013.
124.	Farb MG, Ganley‐Leal L, Mott M, Liang Y, Ercan B, Widlansky ME, Bigornia SJ, Fiscale AJ, Apovian CM, Carmine B, Hess DT, Vita JA, Gokce N. Arteriolar function in visceral adipose tissue is impaired in human obesity. Arterioscler Thromb Vasc Biol 32: 467‐473, 2012.
125.	Feelisch M, Kolb‐Bachofen V, Liu D, Lundberg JO, Revelo LP, Suschek CV, Weller RB. Is sunlight good for our heart? Eur Heart J 31: 1041‐1045, 2010.
126.	Feger GI, Schilling L, Ehrenreich H, Wahl M. Endothelium‐dependent relaxation counteracting the contractile action of endothelin‐1 is partly due to ETB receptor activation. Res Exp Med (Berl) 196: 327‐337, 1997.
127.	Feher A, Rutkai I, Beleznai T, Ungvari Z, Csiszar A, Edes I, Bagi Z. Caveolin‐1 limits the contribution of BK(Ca) channel to EDHF‐mediated arteriolar dilation: Implications in diet‐induced obesity. Cardiovasc Res 87: 732‐739, 2010.
128.	Feigl EO. Coronary physiology. Physiol Rev 63: 1‐205, 1983.
129.	Fellner RC, Cook AK, O'Connor PM, Zhang S, Pollock DM, Inscho EW. High‐salt diet blunts renal autoregulation by a reactive oxygen species‐dependent mechanism. Am J Physiol Renal Physiol 307: F33‐F40, 2014.
130.	Feng J, Damrauer SM, Lee M, Sellke FW, Ferran C, Abid MR. Endothelium‐dependent coronary vasodilatation requires NADPH oxidase‐derived reactive oxygen species. Arterioscler Thromb Vasc Biol 30: 1703‐1710, 2010.
131.	Feron O, Dessy C, Moniotte S, Desager JP, Balligand JL. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 103: 897‐905, 1999.
132.	Finazzi‐Agro A, Menichelli A, Persiani M, Biancini G, Del Principe D. Hydrogen peroxide release from human blood platelets. Biochim Biophys Acta 718: 21‐25, 1982.
133.	Fleming I. Cytochrome p450 and vascular homeostasis. Circ Res 89: 753‐762, 2001.
134.	Fleming I, Michaelis UR, Bredenkotter D, Fisslthaler B, Dehghani F, Brandes RP, Busse R. Endothelium‐derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ Res 88: 44‐51, 2001.
135.	Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: From marvel to menace. Circulation 113: 1708‐1714, 2006.
136.	Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes 26: 77‐82, 2008.
137.	Freed JK, Beyer AM, LoGiudice JA, Hockenberry JC, Gutterman DD. Ceramide changes the mediator of flow‐induced vasodilation from nitric oxide to hydrogen peroxide in the human microcirculation. Circ Res 115: 525‐532, 2014.
138.	Freed JK, Durand MJ, Hoffmann BR, Densmore JC, Greene AS, Gutterman DD. Mitochondria‐regulated formation of endothelial extracellular vesicles shifts the mediator of flow‐induced vasodilation. Am J Physiol Heart Circ Physiol 312 (5): H1096‐H1104, 2017. DOI: 10.1152/ajpheart.00680.2016.
139.	Friederich‐Persson M, Nguyen Dinh Cat A, Persson P, Montezano AC, Touyz RM. Brown adipose tissue regulates small artery function through NADPH oxidase 4‐derived hydrogen peroxide and redox‐sensitive protein kinase G‐1alpha. Arterioscler Thromb Vasc Biol 37: 455‐465, 2017.
140.	Fukai T, Siegfried MR, Ushio‐Fukai M, Cheng Y, Kojda G, Harrison DG. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest 105: 1631‐1639, 2000.
141.	Fukai T, Ushio‐Fukai M. Superoxide dismutases: Role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15: 1583‐1606, 2011.
142.	Garg UC, Hassid A. Nitric oxide‐generating vasodilators and 8‐bromo‐cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83: 1774‐1777, 1989.
143.	Giamouzis G, Schelbert EB, Butler J. Growing evidence linking microvascular dysfunction with heart failure with preserved ejection fraction. J Am Heart Assoc 5: e003259, 2016.
144.	Gianni D, Taulet N, Zhang H, DerMardirossian C, Kister J, Martinez L, Roush WR, Brown SJ, Bokoch GM, Rosen H. A novel and specific NADPH oxidase‐1 (Nox1) small‐molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells. ACS Chem Biol 5: 981‐993, 2010.
145.	Giardina JB, Green GM, Rinewalt AN, Granger JP, Khalil RA. Role of endothelin B receptors in enhancing endothelium‐dependent nitric oxide‐mediated vascular relaxation during high salt diet. Hypertension 37: 516‐523, 2001.
146.	Gimbrone MA Jr, Garcia‐Cardena G. Endothelial cell dysfunction and the pathobiology of Atherosclerosis. Circ Res 118: 620‐636, 2016.
147.	Gioscia‐Ryan RA, LaRocca TJ, Sindler AL, Zigler MC, Murphy MP, Seals DR. Mitochondria‐targeted antioxidant (MitoQ) ameliorates age‐related arterial endothelial dysfunction in mice. J Physiol 592: 2549‐2561, 2014.
148.	Godo S, Sawada A, Saito H, Ikeda S, Enkhjargal B, Suzuki K, Tanaka S, Shimokawa H. Disruption of physiological balance between nitric oxide and endothelium‐dependent hyperpolarization impairs cardiovascular homeostasis in mice. Arterioscler Thromb Vasc Biol 36: 97‐107, 2016.
149.	Godo S, Shimokawa H. Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis. Free Radic Biol Med, 2016.
150.	Goodwill AG, Frisbee SJ, Stapleton PA, James ME, Frisbee JC. Impact of chronic anticholesterol therapy on development of microvascular rarefaction in the metabolic syndrome. Microcirculation 16: 667‐684, 2009.
151.	Granger DN, Rodrigues SF, Yildirim A, Senchenkova EY. Microvascular responses to cardiovascular risk factors. Microcirculation 17: 192‐205, 2010.
152.	Gray SP, Di Marco E, Kennedy K, Chew P, Okabe J, El‐Osta A, Calkin AC, Biessen EA, Touyz RM, Cooper ME, Schmidt HH, Jandeleit‐Dahm KA. Reactive oxygen species can provide atheroprotection via NOX4‐dependent inhibition of inflammation and vascular remodeling. Arterioscler Thromb Vasc Biol 36: 295‐307, 2016.
153.	Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El‐Osta A, Andrews KL, Chin‐Dusting JP, Touyz RM, Wingler K, Cooper ME, Schmidt HH, Jandeleit‐Dahm KA. NADPH oxidase 1 plays a key role in diabetes mellitus‐accelerated atherosclerosis. Circulation 127: 1888‐1902, 2013.
154.	Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA, Heagerty AM. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation 119: 1661‐1670, 2009.
155.	Griendling KK, Sorescu D, Lassegue B, Ushio‐Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20: 2175‐2183, 2000.
156.	Griendling KK, Touyz RM, Zweier JL, Dikalov S, Chilian W, Chen YR, Harrison DG, Bhatnagar A, American Heart Association Council on Basic Cardiovascular Sciences. Measurement of reactive oxygen species, reactive nitrogen species, and redox‐dependent signaling in the cardiovascular system: A scientific statement from the American Heart Association. Circ Res 119: e39‐e75, 2016.
157.	Griffith TM. Endothelium‐dependent smooth muscle hyperpolarization: Do gap junctions provide a unifying hypothesis? Br J Pharmacol 141: 881‐903, 2004.
158.	Grizelj I, Cavka A, Bian JT, Szczurek M, Robinson A, Shinde S, Nguyen V, Braunschweig C, Wang E, Drenjancevic I, Phillips SA. Reduced flow‐and acetylcholine‐induced dilations in visceral compared to subcutaneous adipose arterioles in human morbid obesity. Microcirculation 22: 44‐53, 2015.
159.	Gu X, El‐Remessy AB, Brooks SE, Al‐Shabrawey M, Tsai NT, Caldwell RB. Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite. Am J Physiol Cell Physiol 285: C546‐C554, 2003.
160.	Gutterman DD, Chabowski DS, Kadlec AO, Durand MJ, Freed JK, Ait‐Aissa K, Beyer AM. The human microcirculation: Regulation of flow and beyond. Circ Res 118: 157‐172, 2016.
161.	Gutterman DD, Miura H, Liu Y. Redox modulation of vascular tone: Focus of potassium channel mechanisms of dilation. Arterioscler Thromb Vasc Biol 25: 671‐678, 2005.
162.	Hafstad AD, Nabeebaccus AA, Shah AM. Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 108: 359, 2013.
163.	Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, Nour KR, Quyyumi AA. Prognostic value of coronary vascular endothelial dysfunction. Circulation 106: 653‐658, 2002.
164.	Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E. Overexpression of 15‐lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor‐deficient mice. Arterioscler Thromb Vasc Biol 20: 2100‐2105, 2000.
165.	Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 11: 298‐300, 1956.
166.	Harman D. Free radical theory of aging: An update: Increasing the functional life span. Ann N Y Acad Sci 1067: 10‐21, 2006.
167.	Harrison DG. The mosaic theory revisited: Common molecular mechanisms coordinating diverse organ and cellular events in hypertension. J Am Soc Hypertens 7: 68‐74, 2013.
168.	Hashimoto M, Akishita M, Eto M, Kozaki K, Ako J, Sugimoto N, Yoshizumi M, Toba K, Ouchi Y. The impairment of flow‐mediated vasodilatation in obese men with visceral fat accumulation. Int J Obes Relat Metab Disord 22: 477‐484, 1998.
169.	Hatoum OA, Binion DG, Otterson MF, Gutterman DD. Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide‐mediated vasodilation. Gastroenterology 125: 58‐69, 2003.
170.	Haurani MJ, Cifuentes ME, Shepard AD, Pagano PJ. Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II‐induced adventitial myofibroblast migration. Hypertension 52: 143‐149, 2008.
171.	Hockenberry J, Zinkevitch N, Beyer A, Gutterman D. Acute and chronic inhibition of NOS causes a switch in vasodilator mechanism from nitric oxide to hydrogen peroxide in the human microcirculation. FASEB J 29: 794.792, 2015.
172.	Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, Liu CH, Hwang J, Selzer RH, Azen SP, VEAPS Research Group. Alpha‐tocopherol supplementation in healthy individuals reduces low‐density lipoprotein oxidation but not atherosclerosis: The Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation 106: 1453‐1459, 2002.
173.	Houston M, Estevez A, Chumley P, Aslan M, Marklund S, Parks DA, Freeman BA. Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide‐dependent signaling. J Biol Chem 274: 4985‐4994, 1999.
174.	Howard AB, Alexander RW, Nerem RM, Griendling KK, Taylor WR. Cyclic strain induces an oxidative stress in endothelial cells. Am J Phys 272: C421‐C427, 1997.
175.	Hsieh HJ, Cheng CC, Wu ST, Chiu JJ, Wung BS, Wang DL. Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear‐induced c‐fos expression. J Cell Physiol 175: 156‐162, 1998.
176.	Huang A, Sun D, Kaley G, Koller A. Superoxide released to high intra‐arteriolar pressure reduces nitric oxide‐mediated shear stress‐ and agonist‐induced dilations. Circ Res 83: 960‐965, 1998.
177.	Huang A, Sun D, Shesely EG, Levee EM, Koller A, Kaley G. Neuronal NOS‐dependent dilation to flow in coronary arteries of male eNOS‐KO mice. Am J Physiol Heart Circ Physiol 282: H429‐H436, 2002.
178.	Ikenaga H, Fallet RW, Carmines PK. Basal nitric oxide production curtails arteriolar vasoconstrictor responses to ANG II in rat kidney. Am J Phys 271: F365‐F373, 1996.
179.	Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C‐‐dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939‐1945, 2000.
180.	Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrison DG. Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ Res 79: 32‐37, 1996.
181.	Ito S, Arima S, Ren YL, Juncos LA, Carretero OA. Endothelium‐derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. J Clin Invest 91: 2012‐2019, 1993.
182.	Ito S, Juncos LA, Nushiro N, Johnson CS, Carretero OA. Endothelium‐derived relaxing factor modulates endothelin action in afferent arterioles. Hypertension 17: 1052‐1056, 1991.
183.	Janssens S, Flaherty D, Nong Z, Varenne O, van Pelt N, Haustermans C, Zoldhelyi P, Gerard R, Collen D. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 97: 1274‐1281, 1998.
184.	Jiang F, Roberts SJ, Datla S, Dusting GJ. NO modulates NADPH oxidase function via heme oxygenase‐1 in human endothelial cells. Hypertension 48: 950‐957, 2006.
185.	Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM. Aldosterone mediates angiotensin II‐induced interstitial cardiac fibrosis via a Nox2‐containing NADPH oxidase. FASEB J 20: 1546‐1548, 2006.
186.	Johnson BA, Lowenstein CJ, Schwarz MA, Nakayama DK, Pitt BR, Davies P. Culture of pulmonary microvascular smooth muscle cells from intraacinar arteries of the rat: Characterization and inducible production of nitric oxide. Am J Respir Cell Mol Biol 10: 604‐612, 1994.
187.	Jones CI 3rd, Zhu H, Martin SF, Han Z, Li Y, Alevriadou BR. Regulation of antioxidants and phase 2 enzymes by shear‐induced reactive oxygen species in endothelial cells. Ann Biomed Eng 35: 683‐693, 2007.
188.	Jones CJ, Kuo L, Davis MJ, DeFily DV, Chilian WM. Role of nitric oxide in the coronary microvascular responses to adenosine and increased metabolic demand. Circulation 91: 1807‐1813, 1995.
189.	Jones DP. Redefining oxidative stress. Antioxid Redox Signal 8: 1865‐1879, 2006.
190.	Jonk AM, Houben AJ, de Jongh RT, Serne EH, Schaper NC, Stehouwer CD. Microvascular dysfunction in obesity: A potential mechanism in the pathogenesis of obesity‐associated insulin resistance and hypertension. Physiology (Bethesda) 22: 252‐260, 2007.
191.	Joussen AM, Poulaki V, Qin W, Kirchhof B, Mitsiades N, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. Retinal vascular endothelial growth factor induces intercellular adhesion molecule‐1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol 160: 501‐509, 2002.
192.	Just A, Whitten CL, Arendshorst WJ. Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors. Am J Physiol Renal Physiol 294: F719‐F728, 2008.
193.	Kadlec AO, Chabowski DS, Ait‐Aissa K, Hockenberry JC, Otterson MF, Durand MJ, Freed JK, Beyer AM, Gutterman DD. PGC‐1alpha (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha) overexpression in coronary artery disease recruits NO and hydrogen peroxide during flow‐mediated dilation and protects against increased intraluminal pressure. Hypertension 70: 166‐173, 2017.
194.	Kahler J, Mendel S, Weckmuller J, Orzechowski HD, Mittmann C, Koster R, Paul M, Meinertz T, Munzel T. Oxidative stress increases synthesis of big endothelin‐1 by activation of the endothelin‐1 promoter. J Mol Cell Cardiol 32: 1429‐1437, 2000.
195.	Kang LS, Reyes RA, Muller‐Delp JM. Aging impairs flow‐induced dilation in coronary arterioles: Role of NO and H(2)O(2). Am J Physiol Heart Circ Physiol 297: H1087‐H1095, 2009.
196.	Kang‐Decker N, Cao S, Chatterjee S, Yao J, Egan LJ, Semela D, Mukhopadhyay D, Shah V. Nitric oxide promotes endothelial cell survival signaling through S‐nitrosylation and activation of dynamin‐2. J Cell Sci 120: 492‐501, 2007.
197.	Katakam PV, Tulbert CD, Snipes JA, Erdos B, Miller AW, Busija DW. Impaired insulin‐induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species. Am J Physiol Heart Circ Physiol 288: H854‐H860, 2005.
198.	Kim YW, Byzova TV. Oxidative stress in angiogenesis and vascular disease. Blood 123: 625‐631, 2014.
199.	Kleinschnitz C, Grund H, Wingler K, Armitage ME, Jones E, Mittal M, Barit D, Schwarz T, Geis C, Kraft P, Barthel K, Schuhmann MK, Herrmann AM, Meuth SG, Stoll G, Meurer S, Schrewe A, Becker L, Gailus‐Durner V, Fuchs H, Klopstock T, de Angelis MH, Jandeleit‐Dahm K, Shah AM, Weissmann N, Schmidt HH. Post‐stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol 8: e1000479, 2010.
200.	Kojda G, Harrison D. Interactions between NO and reactive oxygen species: Pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovasc Res 43: 562‐571, 1999.
201.	Kolpakov V, Gordon D, Kulik TJ. Nitric oxide‐generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circ Res 76: 305‐309, 1995.
202.	Konior A, Schramm A, Czesnikiewicz‐Guzik M, Guzik TJ. NADPH oxidases in vascular pathology. Antioxid Redox Signal 20: 2794‐2814, 2014.
203.	Kontos HA, Wei EP, Povlishock JT, Christman CW. Oxygen radicals mediate the cerebral arteriolar dilation from arachidonate and bradykinin in cats. Circ Res 55: 295‐303, 1984.
204.	Kornfeld OS, Hwang S, Disatnik MH, Chen CH, Qvit N, Mochly‐Rosen D. Mitochondrial reactive oxygen species at the heart of the matter: New therapeutic approaches for cardiovascular diseases. Circ Res 116: 1783‐1799, 2015.
205.	Korthuis RJ. Mechanisms of I/R‐induced endothelium‐dependent vasodilator dysfunction. Adv Pharmacol 81: 331‐364, 2018.
206.	Kossenjans W, Rymaszewski Z, Barankiewicz J, Bobst A, Ashraf M. Menadione‐induced oxidative stress in bovine heart microvascular endothelial cells. Microcirculation 3: 39‐47, 1996.
207.	Kowluru RA, Atasi L, Ho YS. Role of mitochondrial superoxide dismutase in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 47: 1594‐1599, 2006.
208.	Kroller‐Schon S, Steven S, Kossmann S, Scholz A, Daub S, Oelze M, Xia N, Hausding M, Mikhed Y, Zinssius E, Mader M, Stamm P, Treiber N, Scharffetter‐Kochanek K, Li H, Schulz E, Wenzel P, Munzel T, Daiber A. Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species‐studies in white blood cells and in animal models. Antioxid Redox Signal 20: 247‐266, 2014.
209.	Kubes P, Granger DN. Nitric oxide modulates microvascular permeability. Am J Phys 262: H611‐H615, 1992.
210.	Kumai Y, Ooboshi H, Ago T, Ishikawa E, Takada J, Kamouchi M, Kitazono T, Ibayashi S, Iida M. Protective effects of angiotensin II type 1 receptor blocker on cerebral circulation independent of blood pressure. Exp Neurol 210: 441‐448, 2008.
211.	Kuo L, Chilian WM, Davis MJ. Interaction of pressure‐ and flow‐induced responses in porcine coronary resistance vessels. Am J Phys 261: H1706‐H1715, 1991.
212.	La Favor JD, Dubis GS, Yan H, White JD, Nelson MA, Anderson EJ, Hickner RC. Microvascular endothelial dysfunction in sedentary, obese humans is mediated by NADPH oxidase: Influence of exercise training. Arterioscler Thromb Vasc Biol 36: 2412‐2420, 2016.
213.	Laakso J, Mervaala E, Himberg JJ, Teravainen TL, Karppanen H, Vapaatalo H, Lapatto R. Increased kidney xanthine oxidoreductase activity in salt‐induced experimental hypertension. Hypertension 32: 902‐906, 1998.
214.	Lacy F, O'Connor DT, Schmid‐Schonbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 16: 291‐303, 1998.
215.	Lakshminarayanan V, Drab‐Weiss EA, Roebuck KA. H2O2 and tumor necrosis factor‐alpha induce differential binding of the redox‐responsive transcription factors AP‐1 and NF‐kappaB to the interleukin‐8 promoter in endothelial and epithelial cells. J Biol Chem 273: 32670‐32678, 1998.
216.	Lamb FS, Webb RC. Vascular effects of free radicals generated by electrical stimulation. Am J Phys 247: H709‐H714, 1984.
217.	Lamkin‐Kennard KA, Buerk DG, Jaron D. Interactions between NO and O2 in the microcirculation: A mathematical analysis. Microvasc Res 68: 38‐50, 2004.
218.	Lamping KG, Nuno DW, Chappell DA, Faraci FM. Agonist‐specific impairment of coronary vascular function in genetically altered, hyperlipidemic mice. Am J Phys 276: R1023‐R1029, 1999.
219.	Lamping KG, Nuno DW, Shesely EG, Maeda N, Faraci FM. Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase‐deficient mice. Am J Physiol Heart Circ Physiol 279: H1906‐H1912, 2000.
220.	Landino LM. Protein thiol modification by peroxynitrite anion and nitric oxide donors. Methods Enzymol 440: 95‐109, 2008.
221.	Larsen BT, Bubolz AH, Mendoza SA, Pritchard KA Jr, Gutterman DD. Bradykinin‐induced dilation of human coronary arterioles requires NADPH oxidase‐derived reactive oxygen species. Arterioscler Thromb Vasc Biol 29: 739‐745, 2009.
222.	Larsen BT, Gutterman DD, Sato A, Toyama K, Campbell WB, Zeldin DC, Manthati VL, Falck JR, Miura H. Hydrogen peroxide inhibits cytochrome p450 epoxygenases: Interaction between two endothelium‐derived hyperpolarizing factors. Circ Res 102: 59‐67, 2008.
223.	Lassegue B, Clempus RE. Vascular NAD(P)H oxidases: Specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285: R277‐R297, 2003.
224.	Lassegue B, San Martin A, Griendling KK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110: 1364‐1390, 2012.
225.	Lauer N, Suvorava T, Ruther U, Jacob R, Meyer W, Harrison DG, Kojda G. Critical involvement of hydrogen peroxide in exercise‐induced up‐regulation of endothelial NO synthase. Cardiovasc Res 65: 254‐262, 2005.
226.	Laurindo FR, Pedro Mde A, Barbeiro HV, Pileggi F, Carvalho MH, Augusto O, da Luz PL. Vascular free radical release. Ex vivo and in vivo evidence for a flow‐dependent endothelial mechanism. Circ Res 74: 700‐709, 1994.
227.	LeBlanc AJ, Moseley AM, Chen BT, Frazer D, Castranova V, Nurkiewicz TR. Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species‐dependent mechanism. Cardiovasc Toxicol 10: 27‐36, 2010.
228.	Lee CU, Hahne G, Hanske J, Bange T, Bier D, Rademacher C, Hennig S, Grossmann TN. Redox modulation of PTEN phosphatase activity by hydrogen peroxide and bisperoxidovanadium complexes. Angew Chem Int Ed Engl 54: 13796‐13800, 2015.
229.	Lee HS, Namkoong K, Kim DH, Kim KJ, Cheong YH, Kim SS, Lee WB, Kim KY. Hydrogen peroxide‐induced alterations of tight junction proteins in bovine brain microvascular endothelial cells. Microvasc Res 68: 231‐238, 2004.
230.	Lee MY, Griendling KK. Redox signaling, vascular function, and hypertension. Antioxid Redox Signal 10: 1045‐1059, 2008.
231.	Lehr HA. Microcirculatory dysfunction induced by cigarette smoking. Microcirculation 7: 367‐384, 2000.
232.	Lehr HA, Frei B, Arfors KE. Vitamin C prevents cigarette smoke‐induced leukocyte aggregation and adhesion to endothelium in vivo. Proc Natl Acad Sci U S A 91: 7688‐7692, 1994.
233.	Lehr HA, Kress E, Menger MD, Friedl HP, Hubner C, Arfors KE, Messmer K. Cigarette smoke elicits leukocyte adhesion to endothelium in hamsters: Inhibition by CuZn‐SOD. Free Radic Biol Med 14: 573‐581, 1993.
234.	Leikert JF, Räthel TR, Müller C, Vollmar AM, Dirsch VM. Reliable in vitro measurement of nitric oxide released from endothelial cells using low concentrations of the fluorescent probe 4,5‐diaminofluorescein. FEBS Lett 506: 131‐134, 2001.
235.	Lenda DM, Boegehold MA. Effect of a high salt diet on microvascular antioxidant enzymes. J Vasc Res 39: 41‐50, 2002.
236.	Lenda DM, Sauls BA, Boegehold MA. Reactive oxygen species may contribute to reduced endothelium‐dependent dilation in rats fed high salt. Am J Physiol Heart Circ Physiol 279: H7‐H14, 2000.
237.	Levy BI, Schiffrin EL, Mourad JJ, Agostini D, Vicaut E, Safar ME, Struijker‐Boudier HA. Impaired tissue perfusion: A pathology common to hypertension, obesity, and diabetes mellitus. Circulation 118: 968‐976, 2008.
238.	Lewis MS, Whatley RE, Cain P, McIntyre TM, Prescott SM, Zimmerman GA. Hydrogen peroxide stimulates the synthesis of platelet‐activating factor by endothelium and induces endothelial cell‐dependent neutrophil adhesion. J Clin Invest 82: 2045‐2055, 1988.
239.	Li H, Chai Q, Gutterman DD, Liu Y. Elevated glucose impairs cAMP‐mediated dilation by reducing Kv channel activity in rat small coronary smooth muscle cells. Am J Physiol Heart Circ Physiol 285: H1213‐H1219, 2003.
240.	Li J, Li W, Su J, Liu W, Altura BT, Altura BM. Hydrogen peroxide induces apoptosis in cerebral vascular smooth muscle cells: Possible relation to neurodegenerative diseases and strokes. Brain Res Bull 62: 101‐106, 2003.
241.	Li L, Fink GD, Watts SW, Northcott CA, Galligan JJ, Pagano PJ, Chen AF. Endothelin‐1 increases vascular superoxide via endothelin(A)‐NADPH oxidase pathway in low‐renin hypertension. Circulation 107: 1053‐1058, 2003.
242.	Li PL, Jin MW, Campbell WB. Effect of selective inhibition of soluble guanylyl cyclase on the K(Ca) channel activity in coronary artery smooth muscle. Hypertension 31: 303‐308, 1998.
243.	Li Q, Fu GB, Zheng JT, He J, Niu XB, Chen QD, Yin Y, Qian X, Xu Q, Wang M, Sun AF, Shu Y, Rui H, Liu LZ, Jiang BH. NADPH oxidase subunit p22(phox)‐mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer. Biochim Biophys Acta 1833: 3375‐3385, 2013.
244.	Li WG, Miller FJ Jr, Zhang HJ, Spitz DR, Oberley LW, Weintraub NL. H(2)O(2)‐induced O(2) production by a non‐phagocytic NAD(P)H oxidase causes oxidant injury. J Biol Chem 276: 29251‐29256, 2001.
245.	Liao JC, Kuo L. Interaction between adenosine and flow‐induced dilation in coronary microvascular network. Am J Phys 272: H1571‐H1581, 1997.
246.	Libby P. Murine "model" monotheism: An iconoclast at the altar of mouse. Circ Res 117: 921‐925, 2015.
247.	Lin SJ, Shyue SK, Liu PL, Chen YH, Ku HH, Chen JW, Tam KB, Chen YL. Adenovirus‐mediated overexpression of catalase attenuates oxLDL‐induced apoptosis in human aortic endothelial cells via AP‐1 and C‐Jun N‐terminal kinase/extracellular signal‐regulated kinase mitogen‐activated protein kinase pathways. J Mol Cell Cardiol 36: 129‐139, 2004.
248.	Liu L, Ruddy TD, Dalipaj M, Szyszkowicz M, You H, Poon R, Wheeler A, Dales R. Influence of personal exposure to particulate air pollution on cardiovascular physiology and biomarkers of inflammation and oxidative stress in subjects with diabetes. J Occup Environ Med 49: 258‐265, 2007.
249.	Liu R, Ren Y, Garvin JL, Carretero OA. Superoxide enhances tubuloglomerular feedback by constricting the afferent arteriole. Kidney Int 66: 268‐274, 2004.
250.	Liu Y, Bubolz AH, Mendoza S, Zhang DX, Gutterman DD. H2O2 is the transferrable factor mediating flow‐induced dilation in human coronary arterioles. Circ Res 108: 566‐573, 2011.
251.	Liu Y, Li H, Bubolz AH, Zhang DX, Gutterman DD. Endothelial cytoskeletal elements are critical for flow‐mediated dilation in human coronary arterioles. Med Biol Eng Comput 46: 469‐478, 2008.
252.	Liu Y, Terata K, Chai Q, Li H, Kleinman LH, Gutterman DD. Peroxynitrite inhibits Ca2+‐activated K+ channel activity in smooth muscle of human coronary arterioles. Circ Res 91: 1070‐1076, 2002.
253.	Liu Y, Zhao H, Li H, Kalyanaraman B, Nicolosi AC, Gutterman DD. Mitochondrial sources of H2O2 generation play a key role in flow‐mediated dilation in human coronary resistance arteries. Circ Res 93: 573‐580, 2003.
254.	Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR, HOPE and HOPE‐TOO Trial Investigators. Effects of long‐term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. JAMA 293: 1338‐1347, 2005.
255.	Loyer X, Gomez AM, Milliez P, Fernandez‐Velasco M, Vangheluwe P, Vinet L, Charue D, Vaudin E, Zhang W, Sainte‐Marie Y, Robidel E, Marty I, Mayer B, Jaisser F, Mercadier JJ, Richard S, Shah AM, Benitah JP, Samuel JL, Heymes C. Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling. Circulation 117: 3187‐3198, 2008.
256.	Lu T, He T, Katusic ZS, Lee HC. Molecular mechanisms mediating inhibition of human large conductance Ca2+‐activated K+ channels by high glucose. Circ Res 99: 607‐616, 2006.
257.	Lubos E, Handy DE, Loscalzo J. Role of oxidative stress and nitric oxide in atherothrombosis. Front Biosci 13: 5323‐5344, 2008.
258.	Lucchesi PA, Belmadani S, Matrougui K. Hydrogen peroxide acts as both vasodilator and vasoconstrictor in the control of perfused mouse mesenteric resistance arteries. J Hypertens 23: 571‐579, 2005.
259.	Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 21: 269‐280, 2006.
260.	Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25: 29‐38, 2005.
261.	Majesky MW, Dong XR, Hoglund V, Daum G, Mahoney WM Jr. The adventitia: A progenitor cell niche for the vessel wall. Cells Tissues Organs 195: 73‐81, 2012.
262.	Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension 54: 1384‐1392, 2009.
263.	Marin C, Delgado‐Lista J, Ramirez R, Carracedo J, Caballero J, Perez‐Martinez P, Gutierrez‐Mariscal FM, Garcia‐Rios A, Delgado‐Casado N, Cruz‐Teno C, Yubero‐Serrano EM, Tinahones F, Malagon Mdel M, Perez‐Jimenez F, Lopez‐Miranda J. Mediterranean diet reduces senescence‐associated stress in endothelial cells. Age (Dordr) 34: 1309‐1316, 2012.
264.	Martinez‐Lemus LA, Hill MA, Bolz SS, Pohl U, Meininger GA. Acute mechanoadaptation of vascular smooth muscle cells in response to continuous arteriolar vasoconstriction: Implications for functional remodeling. FASEB J 18: 708‐710, 2004.
265.	Martinez‐Lemus LA, Zhao G, Galinanes EL, Boone M. Inward remodeling of resistance arteries requires reactive oxygen species‐dependent activation of matrix metalloproteinases. Am J Physiol Heart Circ Physiol 300: H2005‐H2015, 2011.
266.	Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, Takeshita A. Hydrogen peroxide is an endothelium‐derived hyperpolarizing factor in mice. J Clin Invest 106: 1521‐1530, 2000.
267.	Matsumoto A, Mason SR, Flatscher‐Bader T, Ward LC, Marsh SA, Wilce PA, Fassett RG, de Haan JB, Coombes JS. Effects of exercise and antioxidant supplementation on endothelial gene expression. Int J Cardiol 158: 59‐65, 2012.
268.	Mattson DL. Infiltrating immune cells in the kidney in salt‐sensitive hypertension and renal injury. Am J Physiol Renal Physiol 307: F499‐F508, 2014.
269.	Mayer‐Davis EJ, Bell RA, Reboussin BA, Rushing J, Marshall JA, Hamman RF. Antioxidant nutrient intake and diabetic retinopathy: The San Luis Valley Diabetes Study. Ophthalmology 105: 2264‐2270, 1998.
270.	Mayhan WG, Sharpe GM. Chronic exposure to nicotine alters endothelium‐dependent arteriolar dilatation: Effect of superoxide dismutase. J Appl Physiol (1985) 86: 1126‐1134, 1999.
271.	Micha R, Imamura F, Wyler von Ballmoos M, Solomon DH, Hernán MA, Ridker PM, Mozaffarian D. Systematic review and meta‐analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 108: 1362‐1370, 2011.
272.	Mikus CR, Rector RS, Arce‐Esquivel AA, Libla JL, Booth FW, Ibdah JA, Laughlin MH, Thyfault JP. Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long‐Evans Tokushima Fatty rats. J Appl Physiol (1985) 109: 1203‐1210, 2010.
273.	Miller FJ Jr, Dellsperger KC, Gutterman DD. Pharmacologic activation of the human coronary microcirculation in vitro: Endothelium‐dependent dilation and differential responses to acetylcholine. Cardiovasc Res 38: 744‐750, 1998.
274.	Minor RL Jr, Myers PR, Guerra R Jr, Bates JN, Harrison DG. Diet‐induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 86: 2109‐2116, 1990.
275.	Miura H, Liu Y, Gutterman DD. Human coronary arteriolar dilation to bradykinin depends on membrane hyperpolarization: Contribution of nitric oxide and Ca2+‐activated K+ channels. Circulation 99: 3132‐3138, 1999.
276.	Miura H, Wachtel RE, Loberiza FR Jr, Saito T, Miura M, Nicolosi AC, Gutterman DD. Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: Reduced activity of ATP‐sensitive potassium channels. Circ Res 92: 151‐158, 2003.
277.	Momma K, Toyono M. The role of nitric oxide in dilating the fetal ductus arteriosus in rats. Pediatr Res 46: 311‐315, 1999.
278.	Moncada S, Higgs EA. The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 147 (Suppl 1): S193‐S201, 2006.
279.	Morita I. Distinct functions of COX‐1 and COX‐2. Prostaglandins Other Lipid Mediat 68‐69: 165‐175, 2002.
280.	Moro MA, Darley‐Usmar VM, Lizasoain I, Su Y, Knowles RG, Radomski MW, Moncada S. The formation of nitric oxide donors from peroxynitrite. Br J Pharmacol 116: 1999‐2004, 1995.
281.	Morton JS, Rueda‐Clausen CF, Davidge ST. Mechanisms of endothelium‐dependent vasodilation in male and female, young and aged offspring born growth restricted. Am J Physiol Regul Integr Comp Physiol 298: R930‐R938, 2010.
282.	Mowbray AL, Kang DH, Rhee SG, Kang SW, Jo H. Laminar shear stress up‐regulates peroxiredoxins (PRX) in endothelial cells: PRX 1 as a mechanosensitive antioxidant. J Biol Chem 283: 1622‐1627, 2008.
283.	Mugge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG. Chronic treatment with polyethylene‐glycolated superoxide dismutase partially restores endothelium‐dependent vascular relaxations in cholesterol‐fed rabbits. Circ Res 69: 1293‐1300, 1991.
284.	Mukherjee TK, Mukhopadhyay S, Hoidal JR. The role of reactive oxygen species in TNFalpha‐dependent expression of the receptor for advanced glycation end products in human umbilical vein endothelial cells. Biochim Biophys Acta 1744: 213‐223, 2005.
285.	Murdoch CE, Chaubey S, Zeng L, Yu B, Ivetic A, Walker SJ, Vanhoutte D, Heymans S, Grieve DJ, Cave AC, Brewer AC, Zhang M, Shah AM. Endothelial NADPH oxidase‐2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial‐mesenchymal transition. J Am Coll Cardiol 63: 2734‐2741, 2014.
286.	Myers PR, Banitt PF, Guerra R Jr, Harrison DG. Characteristics of canine coronary resistance arteries: Importance of endothelium. Am J Phys 257: H603‐H610, 1989.
287.	Myers PR, Banitt PF, Guerra R Jr, Harrison DG. Role of the endothelium in modulation of the acetylcholine vasoconstrictor response in porcine coronary microvessels. Cardiovasc Res 25: 129‐137, 1991.
288.	Nanobashvili J, Jozkowicz A, Neumayer C, Fügl A, Sporn E, Polterauer P, Huk I. Comparison of angiogenic potential of human microvascular endothelial cells and human umbilical vein endothelial cells. Eur Surg 35: 214‐219, 2003.
289.	Natarajan R, Fisher BJ, Fowler AA 3rd. Regulation of hypoxia inducible factor‐1 by nitric oxide in contrast to hypoxia in microvascular endothelium. FEBS Lett 549: 99‐104, 2003.
290.	Nediani C, Raimondi L, Borchi E, Cerbai E. Nitric oxide/reactive oxygen species generation and nitroso/redox imbalance in heart failure: From molecular mechanisms to therapeutic implications. Antioxid Redox Signal 14: 289‐331, 2011.
291.	Negash S, Gao Y, Zhou W, Liu J, Chinta S, Raj JU. Regulation of cGMP‐dependent protein kinase‐mediated vasodilation by hypoxia‐induced reactive species in ovine fetal pulmonary veins. Am J Physiol Lung Cell Mol Physiol 293: L1012‐L1020, 2007.
292.	Neri Serneri GG, Coppo M, Bandinelli M, Paoletti P, Toscano T, Micalizzi E, Chiostri M, Boddi M. Exaggerated myocardial oxLDL amount and LOX‐1 receptor over‐expression associated with coronary microvessel inflammation in unstable angina. Atherosclerosis 226: 476‐482, 2013.
293.	Nishijima Y, Cao S, Chabowski DS, Korishettar A, Ge A, Zheng X, Sparapani R, Gutterman DD, Zhang DX. Contribution of KV1.5 channel to hydrogen peroxide‐induced human arteriolar dilation and its modulation by coronary artery disease. Circ Res 120: 658‐669, 2017.
294.	Nishijima Y, Zhang D. H2O2‐induced dilation in human adipose arterioles: Role of smooth muscle K+ channels. FASEB J 29: 637.634, 2015.
295.	Nishikawa Y, Stepp DW, Chilian WM. Nitric oxide exerts feedback inhibition on EDHF‐induced coronary arteriolar dilation in vivo. Am J Physiol Heart Circ Physiol 279: H459‐H465, 2000.
296.	Nojiri H, Shimizu T, Funakoshi M, Yamaguchi O, Zhou H, Kawakami S, Ohta Y, Sami M, Tachibana T, Ishikawa H, Kurosawa H, Kahn RC, Otsu K, Shirasawa T. Oxidative stress causes heart failure with impaired mitochondrial respiration. J Biol Chem 281: 33789‐33801, 2006.
297.	Obrosova IG, Drel VR, Oltman CL, Mashtalir N, Tibrewala J, Groves JT, Yorek MA. Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin‐diabetic rats. Am J Physiol Endocrinol Metab 293: E1645‐E1655, 2007.
298.	Oelze M, Kroller‐Schon S, Steven S, Lubos E, Doppler C, Hausding M, Tobias S, Brochhausen C, Li H, Torzewski M, Wenzel P, Bachschmid M, Lackner KJ, Schulz E, Munzel T, Daiber A. Glutathione peroxidase‐1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. Hypertension 63: 390‐396, 2014.
299.	Ohanyan V, Yin L, Bardakjian R, Kolz C, Enrick M, Hakobyan T, Kmetz J, Bratz I, Luli J, Nagane M, Khan N, Hou H, Kuppusamy P, Graham J, Fu FK, Janota D, Oyewumi MO, Logan S, Lindner JR, Chilian WM. Requisite role of Kv1.5 channels in coronary metabolic dilation. Circ Res 117: 612‐621, 2015.
300.	Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91: 2546‐2551, 1993.
301.	Ohyama K, Matsumoto Y, Takanami K, Ota H, Nishimiya K, Sugisawa J, Tsuchiya S, Amamizu H, Uzuka H, Suda A, Shindo T, Kikuchi Y, Hao K, Tsuburaya R, Takahashi J, Miyata S, Sakata Y, Takase K, Shimokawa H. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. J Am Coll Cardiol 71: 414‐425, 2018.
302.	Okamoto E, Couse T, De Leon H, Vinten‐Johansen J, Goodman RB, Scott NA, Wilcox JN. Perivascular inflammation after balloon angioplasty of porcine coronary arteries. Circulation 104: 2228‐2235, 2001.
303.	Oltman CL, Davidson EP, Coppey LJ, Kleinschmidt TL, Lund DD, Yorek MA. Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin. Obesity (Silver Spring) 16: 82‐89, 2008.
304.	Oltman CL, Richou LL, Davidson EP, Coppey LJ, Lund DD, Yorek MA. Progression of coronary and mesenteric vascular dysfunction in Zucker obese and Zucker diabetic fatty rats. Am J Physiol Heart Circ Physiol 291: H1780‐H1787, 2006.
305.	Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334: 1150‐1155, 1996.
306.	O'Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution‐associated impairment in vascular reactivity and endothelial function. Circulation 111: 2913‐2920, 2005.
307.	Oplander C, Volkmar CM, Paunel‐Gorgulu A, van Faassen EE, Heiss C, Kelm M, Halmer D, Murtz M, Pallua N, Suschek CV. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates. Circ Res 105: 1031‐1040, 2009.
308.	Padmaja S, Huie RE. The reaction of nitric oxide with organic peroxyl radicals. Biochem Biophys Res Commun 195: 539‐544, 1993.
309.	Pagano PJ, Clark JK, Cifuentes‐Pagano ME, Clark SM, Callis GM, Quinn MT. Localization of a constitutively active, phagocyte‐like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II. Proc Natl Acad Sci U S A 94: 14483‐14488, 1997.
310.	Pande J, Dimmers G, Akolkar G, Skelley L, Samson SE, Grover AK. Store operated Ca2+ entry dependent contraction of coronary artery smooth muscle: Inhibition by peroxide pretreatment. Cell Calcium 51: 149‐154, 2012.
311.	Parenti A, Morbidelli L, Cui XL, Douglas JG, Hood JD, Granger HJ, Ledda F, Ziche M. Nitric oxide is an upstream signal of vascular endothelial growth factor‐induced extracellular signal‐regulated kinase1/2 activation in postcapillary endothelium. J Biol Chem 273: 4220‐4226, 1998.
312.	Paulus WJ, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62: 263‐271, 2013.
313.	Payne GA, Borbouse L, Bratz IN, Roell WC, Bohlen HG, Dick GM, Tune JD. Endogenous adipose‐derived factors diminish coronary endothelial function via inhibition of nitric oxide synthase. Microcirculation 15: 417‐426, 2008.
314.	Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol 55: 2825‐2832, 2010.
315.	Persson MG, Gustafsson LE, Wiklund NP, Hedqvist P, Moncada S. Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo. Br J Pharmacol 100: 463‐466, 1990.
316.	Phillips SA, Hatoum OA, Gutterman DD. The mechanism of flow‐induced dilation in human adipose arterioles involves hydrogen peroxide during CAD. Am J Physiol Heart Circ Physiol 292: H93‐H100, 2007.
317.	Pires PW, Earley S. Redox regulation of transient receptor potential channels in the endothelium. Microcirculation 24(3): e12329, 2017.
318.	Pogoda K, Kameritsch P, Retamal MA, Vega JL. Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: A revision. BMC Cell Biol 17 (Suppl 1): 11, 2016.
319.	Poole LB, Nelson KJ. Discovering mechanisms of signaling‐mediated cysteine oxidation. Curr Opin Chem Biol 12: 18‐24, 2008.
320.	Priestley JR, Buelow MW, McEwen ST, Weinberg BD, Delaney M, Balus SF, Hoeppner C, Dondlinger L, Lombard JH. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles. Microvasc Res 89: 134‐145, 2013.
321.	Prieto D, Rivera L, Benedito S, Recio P, Villalba N, Hernandez M, Garcia‐Sacristan A. Ca2+‐activated K+ (KCa) channels are involved in the relaxations elicited by sildenafil in penile resistance arteries. Eur J Pharmacol 531: 232‐237, 2006.
322.	Qamirani E, Ren Y, Kuo L, Hein TW. C‐reactive protein inhibits endothelium‐dependent NO‐mediated dilation in coronary arterioles by activating p38 kinase and NAD(P)H oxidase. Arterioscler Thromb Vasc Biol 25: 995‐1001, 2005.
323.	Quintero M, Colombo SL, Godfrey A, Moncada S. Mitochondria as signaling organelles in the vascular endothelium. Proc Natl Acad Sci U S A 103: 5379‐5384, 2006.
324.	Raaz U, Toh R, Maegdefessel L, Adam M, Nakagami F, Emrich FC, Spin JM, Tsao PS. Hemodynamic regulation of reactive oxygen species: Implications for vascular diseases. Antioxid Redox Signal 20: 914‐928, 2014.
325.	Ramos CL, Pou S, Britigan BE, Cohen MS, Rosen GM. Spin trapping evidence for myeloperoxidase‐dependent hydroxyl radical formation by human neutrophils and monocytes. J Biol Chem 267: 8307‐8312, 1992.
326.	Rao GN, Berk BC. Active oxygen species stimulate vascular smooth muscle cell growth and proto‐oncogene expression. Circ Res 70: 593‐599, 1992.
327.	Rao GN, Runge MS, Alexander RW. Hydrogen peroxide activation of cytosolic phospholipase A2 in vascular smooth muscle cells. Biochim Biophys Acta 1265: 67‐72, 1995.
328.	Ray R, Murdoch CE, Wang M, Santos CX, Zhang M, Alom‐Ruiz S, Anilkumar N, Ouattara A, Cave AC, Walker SJ, Grieve DJ, Charles RL, Eaton P, Brewer AC, Shah AM. Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol 31: 1368‐1376, 2011.
329.	Redlich CA, Chung JS, Cullen MR, Blaner WS, Van Bennekum AM, Berglund L. Effect of long‐term beta‐carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET). Atherosclerosis 145: 425‐432, 1999.
330.	Reis SE, Holubkov R, Lee JS, Sharaf B, Reichek N, Rogers WJ, Walsh EG, Fuisz AR, Kerensky R, Detre KM, Sopko G, Pepine CJ. Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol 33: 1469‐1475, 1999.
331.	Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(‐) and systolic blood pressure in mice. Circ Res 89: 408‐414, 2001.
332.	Rey FE, Pagano PJ. The reactive adventitia: Fibroblast oxidase in vascular function. Arterioscler Thromb Vasc Biol 22: 1962‐1971, 2002.
333.	Rezende F, Lowe O, Helfinger V, Prior KK, Walter M, Zukunft S, Fleming I, Weissmann N, Brandes RP, Schroder K. Unchanged NADPH oxidase activity in Nox1‐Nox2‐Nox4 triple knockout mice: What do NADPH‐stimulated chemiluminescence assays really detect? Antioxid Redox Signal 24: 392‐399, 2016.
334.	Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida‐Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377: 1119‐1131, 2017.
335.	Rizzoni D, Porteri E, Boari GE, De Ciuceis C, Sleiman I, Muiesan ML, Castellano M, Miclini M, Agabiti‐Rosei E. Prognostic significance of small‐artery structure in hypertension. Circulation 108: 2230‐2235, 2003.
336.	Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280: 1763‐1766, 1998.
337.	Robinson AT, Franklin NC, Norkeviciute E, Bian JT, Babana JC, Szczurek MR, Phillips SA. Improved arterial flow‐mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training. J Hypertens 34: 1309‐1316, 2016.
338.	Rogers PA, Chilian WM, Bratz IN, Bryan RM Jr, Dick GM. H2O2 activates redox‐ and 4‐aminopyridine‐sensitive Kv channels in coronary vascular smooth muscle. Am J Physiol Heart Circ Physiol 292: H1404‐H1411, 2007.
339.	Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 364: 362, 1993.
340.	Rosen GM, Freeman BA. Detection of superoxide generated by endothelial cells. Proc Natl Acad Sci U S A 81: 7269‐7273, 1984.
341.	Ross J, Armstead WM. Differential role of PTK and ERK MAPK in superoxide impairment of KATP and KCa channel cerebrovasodilation. Am J Physiol Regul Integr Comp Physiol 285: R149‐R154, 2003.
342.	Saitoh S, Kiyooka T, Rocic P, Rogers PA, Zhang C, Swafford A, Dick GM, Viswanathan C, Park Y, Chilian WM. Redox‐dependent coronary metabolic dilation. Am J Physiol Heart Circ Physiol 293: H3720‐H3725, 2007.
343.	Saitoh S, Zhang C, Tune JD, Potter B, Kiyooka T, Rogers PA, Knudson JD, Dick GM, Swafford A, Chilian WM. Hydrogen peroxide: A feed‐forward dilator that couples myocardial metabolism to coronary blood flow. Arterioscler Thromb Vasc Biol 26: 2614‐2621, 2006.
344.	Salari H, Braquet P, Borgeat P. Comparative effects of indomethacin, acetylenic acids, 15‐HETE, nordihydroguaiaretic acid and BW755C on the metabolism of arachidonic acid in human leukocytes and platelets. Prostaglandins Leukot Med 13: 53‐60, 1984.
345.	Salomon C, Ryan J, Sobrevia L, Kobayashi M, Ashman K, Mitchell M, Rice GE. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLoS One 8: e68451, 2013.
346.	Sampson JB, Beckman JS. Hydrogen peroxide damages the zinc‐binding site of zinc‐deficient Cu, Zn superoxide dismutase. Arch Biochem Biophys 392: 8‐13, 2001.
347.	Sandberg EM, Sayeski PP. Jak2 tyrosine kinase mediates oxidative stress‐induced apoptosis in vascular smooth muscle cells. J Biol Chem 279: 34547‐34552, 2004.
348.	Sanders SP, Zweier JL, Kuppusamy P, Harrison SJ, Bassett DJ, Gabrielson EW, Sylvester JT. Hyperoxic sheep pulmonary microvascular endothelial cells generate free radicals via mitochondrial electron transport. J Clin Invest 91: 46‐52, 1993.
349.	Santiago E, Climent B, Munoz M, Garcia‐Sacristan A, Rivera L, Prieto D. Hydrogen peroxide activates store‐operated Ca(2+) entry in coronary arteries. Br J Pharmacol 172: 5318‐5332, 2015.
350.	Santos JM, Mohammad G, Zhong Q, Kowluru RA. Diabetic retinopathy, superoxide damage and antioxidants. Curr Pharm Biotechnol 12: 352‐361, 2011.
351.	Sarkar R, Meinberg EG, Stanley JC, Gordon D, Webb RC. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ Res 78: 225‐230, 1996.
352.	Schlager O, Willfort‐Ehringer A, Hammer A, Steiner S, Fritsch M, Giurgea A, Margeta C, Lilaj I, Zehetmayer S, Widhalm K, Koppensteiner R, Gschwandtner ME. Microvascular function is impaired in children with morbid obesity. Vasc Med 16: 97‐102, 2011.
353.	Schnackenberg CG. Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature. Am J Physiol Regul Integr Comp Physiol 282: R335‐R342, 2002.
354.	Schroder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, Kruse C, Luedike P, Michaelis UR, Weissmann N, Dimmeler S, Shah AM, Brandes RP. Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res 110: 1217‐1225, 2012.
355.	Scioli MG, Bielli A, Arcuri G, Ferlosio A, Orlandi A. Ageing and microvasculature. Vasc Cell 6: 19, 2014.
356.	Secomb TW. Hemodynamics. Compr Physiol 6: 975‐1003, 2016.
357.	Sedeek MH, Llinas MT, Drummond H, Fortepiani L, Abram SR, Alexander BT, Reckelhoff JF, Granger JP. Role of reactive oxygen species in endothelin‐induced hypertension. Hypertension 42: 806‐810, 2003.
358.	Selemidis S, Dusting GJ, Peshavariya H, Kemp‐Harper BK, Drummond GR. Nitric oxide suppresses NADPH oxidase‐dependent superoxide production by S‐nitrosylation in human endothelial cells. Cardiovasc Res 75: 349‐358, 2007.
359.	Serne EH, Stehouwer CD, ter Maaten JC, ter Wee PM, Rauwerda JA, Donker AJ, Gans RO. Microvascular function relates to insulin sensitivity and blood pressure in normal subjects. Circulation 99: 896‐902, 1999.
360.	Shafique E, Torina A, Reichert K, Colantuono B, Nur N, Zeeshan K, Ravichandran V, Liu Y, Feng J, Zeeshan K, Benjamin LE, Irani K, Harrington EO, Sellke FW, Abid MR. Mitochondrial redox plays a critical role in the paradoxical effects of NAPDH oxidase‐derived ROS on coronary endothelium. Cardiovasc Res 113 (2): 234‐246, 2017.
361.	Shao R, Guo X. Human microvascular endothelial cells immortalized with human telomerase catalytic protein: A model for the study of in vitro angiogenesis. Biochem Biophys Res Commun 321: 788‐794, 2004.
362.	Sheng L, Jiao B, Shao L, Bi S, Cheng C, Zhang J, Jiang Y. Probucol inhibits hydrogen peroxide to induce apoptosis of vascular smooth muscle cells. Mol Med Rep 7: 1185‐1190, 2013.
363.	Shilo S, Roy S, Khanna S, Sen CK. Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells. Arterioscler Thromb Vasc Biol 28: 471‐477, 2008.
364.	Shimokawa H, Godo S. Diverse functions of endothelial NO synthases system: NO and EDH. J Cardiovasc Pharmacol 67: 361‐366, 2016.
365.	Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A. The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium‐dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28: 703‐711, 1996.
366.	Sikora A, Zielonka J, Lopez M, Joseph J, Kalyanaraman B. Direct oxidation of boronates by peroxynitrite: Mechanism and implications in fluorescence imaging of peroxynitrite. Free Radic Biol Med 47: 1401‐1407, 2009.
367.	Souchard JP, Barbacanne MA, Margeat E, Maret A, Nepveu F, Arnal JF. Electron spin resonance detection of extracellular superoxide anion released by cultured endothelial cells. Free Radic Res 29: 441‐449, 1998.
368.	Springer ML, Ozawa CR, Banfi A, Kraft PE, Ip TK, Brazelton TR, Blau HM. Localized arteriole formation directly adjacent to the site of VEGF‐induced angiogenesis in muscle. Mol Ther 7: 441‐449, 2003.
369.	Staiculescu MC, Foote C, Meininger GA, Martinez‐Lemus LA. The role of reactive oxygen species in microvascular remodeling. Int J Mol Sci 15: 23792‐23835, 2014.
370.	Steinhubl SR. Why have antioxidants failed in clinical trials? Am J Cardiol 101: S14‐S19, 2008.
371.	Stralin P, Karlsson K, Johansson BO, Marklund SL. The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. Arterioscler Thromb Vasc Biol 15: 2032‐2036, 1995.
372.	Sturrock A, Cahill B, Norman K, Huecksteadt TP, Hill K, Sanders K, Karwande SV, Stringham JC, Bull DA, Gleich M, Kennedy TP, Hoidal JR. Transforming growth factor‐beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species‐dependent proliferation in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 290: L661‐L673, 2006.
373.	Sugamura K, Keaney JF Jr. Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51: 978‐992, 2011.
374.	Sun D, Huang A, Sharma S, Koller A, Kaley G. Endothelial microtubule disruption blocks flow‐dependent dilation of arterioles. Am J Physiol Heart Circ Physiol 280: H2087‐H2093, 2001.
375.	Sun L, Yau HY, Lau OC, Huang Y, Yao X. Effect of hydrogen peroxide and superoxide anions on cytosolic Ca2+: Comparison of endothelial cells from large‐sized and small‐sized arteries. PLoS One 6: e25432, 2011.
376.	Sun Y, Sumi D, Kumagai Y. Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6‐trinitrotoluene through PI3K/Akt signaling in endothelial cells. Toxicol Appl Pharmacol 214: 55‐60, 2006.
377.	Suresh K, Servinsky L, Reyes J, Baksh S, Undem C, Caterina M, Pearse DB, Shimoda LA. Hydrogen peroxide‐induced calcium influx in lung microvascular endothelial cells involves TRPV4. Am J Physiol Lung Cell Mol Physiol 309: L1467‐L1477, 2015.
378.	Suzuki H, DeLano FA, Parks DA, Jamshidi N, Granger DN, Ishii H, Suematsu M, Zweifach BW, Schmid‐Schonbein GW. Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. Proc Natl Acad Sci U S A 95: 4754‐4759, 1998.
379.	Suzuki H, Swei A, Zweifach BW, Schmid‐Schonbein GW. In vivo evidence for microvascular oxidative stress in spontaneously hypertensive rats. Hydroethidine microfluorography. Hypertension 25: 1083‐1089, 1995.
380.	Takaki A, Morikawa K, Tsutsui M, Murayama Y, Tekes E, Yamagishi H, Ohashi J, Yada T, Yanagihara N, Shimokawa H. Crucial role of nitric oxide synthases system in endothelium‐dependent hyperpolarization in mice. J Exp Med 205: 2053‐2063, 2008.
381.	Tang XD, Garcia ML, Heinemann SH, Hoshi T. Reactive oxygen species impair Slo1 BK channel function by altering cysteine‐mediated calcium sensing. Nat Struct Mol Biol 11: 171‐178, 2004.
382.	Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: Molecular and cellular mechanisms. Hypertension 42: 1075‐1081, 2003.
383.	Tanner MJ, Wang J, Ying R, Suboc TB, Malik M, Couillard A, Branum A, Puppala V, Widlansky ME. Dynamin‐related protein 1 mediates low glucose‐induced endothelial dysfunction in human arterioles. Am J Physiol Heart Circ Physiol 312: H515‐H527, 2017.
384.	ten Freyhaus H, Huntgeburth M, Wingler K, Schnitker J, Baumer AT, Vantler M, Bekhite MM, Wartenberg M, Sauer H, Rosenkranz S. Novel Nox inhibitor VAS2870 attenuates PDGF‐dependent smooth muscle cell chemotaxis, but not proliferation. Cardiovasc Res 71: 331‐341, 2006.
385.	Thengchaisri N, Hein TW, Ren Y, Kuo L. Endothelin‐1 impairs coronary arteriolar dilation: Role of p38 kinase‐mediated superoxide production from NADPH oxidase. J Mol Cell Cardiol 86: 75‐84, 2015.
386.	Thengchaisri N, Hein TW, Wang W, Xu X, Li Z, Fossum TW, Kuo L. Upregulation of arginase by H2O2 impairs endothelium‐dependent nitric oxide‐mediated dilation of coronary arterioles. Arterioscler Thromb Vasc Biol 26: 2035‐2042, 2006.
387.	Thengchaisri N, Kuo L. Hydrogen peroxide induces endothelium‐dependent and ‐independent coronary arteriolar dilation: Role of cyclooxygenase and potassium channels. Am J Physiol Heart Circ Physiol 285: H2255‐H2263, 2003.
388.	Thomas DD, Liu X, Kantrow SP, Lancaster JR Jr. The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci U S A 98: 355‐360, 2001.
389.	Thomas S, Kotamraju S, Zielonka J, Harder DR, Kalyanaraman B. Hydrogen peroxide induces nitric oxide and proteosome activity in endothelial cells: A bell‐shaped signaling response. Free Radic Biol Med 42: 1049‐1061, 2007.
390.	Thompson A, Temple NJ. The case for statins: Has it really been made? J R Soc Med 97: 461‐464, 2004.
391.	Thorup C, Kornfeld M, Winaver JM, Goligorsky MS, Moore LC. Angiotensin‐II stimulates nitric oxide release in isolated perfused renal resistance arteries. Pflugers Arch 435: 432‐434, 1998.
392.	Tieu BC, Ju X, Lee C, Sun H, Lejeune W, Recinos A 3rd, Brasier AR, Tilton RG. Aortic adventitial fibroblasts participate in angiotensin‐induced vascular wall inflammation and remodeling. J Vasc Res 48: 261‐272, 2011.
393.	Tilton RG. Diabetic vascular dysfunction: Links to glucose‐induced reductive stress and VEGF. Microsc Res Tech 57: 390‐407, 2002.
394.	Tilton RG, Kawamura T, Chang KC, Ido Y, Bjercke RJ, Stephan CC, Brock TA, Williamson JR. Vascular dysfunction induced by elevated glucose levels in rats is mediated by vascular endothelial growth factor. J Clin Invest 99: 2192‐2202, 1997.
395.	Tiruppathi C, Naqvi T, Wu Y, Vogel SM, Minshall RD, Malik AB. Albumin mediates the transcytosis of myeloperoxidase by means of caveolae in endothelial cells. Proc Natl Acad Sci U S A 101: 7699‐7704, 2004.
396.	Touyz RM. Reactive oxygen species and angiotensin II signaling in vascular cells – implications in cardiovascular disease. Braz J Med Biol Res 37: 1263‐1273, 2004.
397.	Touyz RM, Chen X, Tabet F, Yao G, He G, Quinn MT, Pagano PJ, Schiffrin EL. Expression of a functionally active gp91phox‐containing neutrophil‐type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: Regulation by angiotensin II. Circ Res 90: 1205‐1213, 2002.
398.	Touyz RM, Yao G, Quinn MT, Pagano PJ, Schiffrin EL. p47phox associates with the cytoskeleton through cortactin in human vascular smooth muscle cells: Role in NAD(P)H oxidase regulation by angiotensin II. Arterioscler Thromb Vasc Biol 25: 512‐518, 2005.
399.	Treasure CB, Vita JA, Cox DA, Fish RD, Gordon JB, Mudge GH, Colucci WS, Sutton MG, Selwyn AP, Alexander RW, Ganz P. Endothelium‐dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. Circulation 81: 772‐779, 1990.
400.	True AL, Rahman A, Malik AB. Activation of NF‐kappaB induced by H(2)O(2) and TNF‐alpha and its effects on ICAM‐1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol 279: L302‐L311, 2000.
401.	Tsutsui M, Onoue H, Iida Y, Smith L, O'Brien T, Katusic ZS. Adventitia‐dependent relaxations of canine basilar arteries transduced with recombinant eNOS gene. Am J Phys 276: H1846‐H1852, 1999.
402.	Tune JD, Richmond KN, Gorman MW, Olsson RA, Feigl EO. Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise. Am J Physiol Heart Circ Physiol 278: H74‐H84, 2000.
403.	Ungvari Z, Csiszar A, Kaminski PM, Wolin MS, Koller A. Chronic high pressure‐induced arterial oxidative stress: Involvement of protein kinase C‐dependent NAD(P)H oxidase and local renin‐angiotensin system. Am J Pathol 165: 219‐226, 2004.
404.	Ursino M, Lodi CA. Interaction among autoregulation, CO2 reactivity, and intracranial pressure: A mathematical model. Am J Phys 274: H1715‐H1728, 1998.
405.	Usatyuk PV, Vepa S, Watkins T, He D, Parinandi NL, Natarajan V. Redox regulation of reactive oxygen species‐induced p38 MAP kinase activation and barrier dysfunction in lung microvascular endothelial cells. Antioxid Redox Signal 5: 723‐730, 2003.
406.	Ushio‐Fukai M. Redox signaling in angiogenesis: Role of NADPH oxidase. Cardiovasc Res 71: 226‐235, 2006.
407.	Ushio‐Fukai M, Alexander RW, Akers M, Yin Q, Fujio Y, Walsh K, Griendling KK. Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J Biol Chem 274: 22699‐22704, 1999.
408.	van de Hoef TP, van Lavieren MA, Damman P, Delewi R, Piek MA, Chamuleau SA, Voskuil M, Henriques JP, Koch KT, de Winter RJ, Spaan JA, Siebes M, Tijssen JG, Meuwissen M, Piek JJ. Physiological basis and long‐term clinical outcome of discordance between fractional flow reserve and coronary flow velocity reserve in coronary stenoses of intermediate severity. Circ Cardiovasc Interv 7: 301‐311, 2014.
409.	Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty years of saying no: Sources, fate, actions, and misfortunes of the endothelium‐derived vasodilator mediator. Circ Res 119: 375‐396, 2016.
410.	Vásquez‐Vivar J, Hogg N, Pritchard KA, Martasek P, Kalyanaraman B. Superoxide anion formation from lucigenin: An electron spin resonance spin‐trapping study. FEBS Lett 403: 127‐130, 1997.
411.	Vecchione C, Carnevale D, Di Pardo A, Gentile MT, Damato A, Cocozza G, Antenucci G, Mascio G, Bettarini U, Landolfi A, Iorio L, Maffei A, Lembo G. Pressure‐induced vascular oxidative stress is mediated through activation of integrin‐linked kinase 1/betaPIX/Rac‐1 pathway. Hypertension 54: 1028‐1034, 2009.
412.	Velmurugan GV, Sundaresan NR, Gupta MP, White C. Defective Nrf2‐dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes. Cardiovasc Res 100: 143‐150, 2013.
413.	Virdis A, Santini F, Colucci R, Duranti E, Salvetti G, Rugani I, Segnani C, Anselmino M, Bernardini N, Blandizzi C, Salvetti A, Pinchera A, Taddei S. Vascular generation of tumor necrosis factor‐alpha reduces nitric oxide availability in small arteries from visceral fat of obese patients. J Am Coll Cardiol 58: 238‐247, 2011.
414.	Vitiello L, Spoletini I, Gorini S, Pontecorvo L, Ferrari D, Ferraro E, Stabile E, Caprio M, la Sala A. Microvascular inflammation in atherosclerosis. IJC Metab Endocr 3: 1‐7, 2014.
415.	Wang D, Chabrashvili T, Wilcox CS. Enhanced contractility of renal afferent arterioles from angiotensin‐infused rabbits: Roles of oxidative stress, thromboxane prostanoid receptors, and endothelium. Circ Res 94: 1436‐1442, 2004.
416.	Wassmann S, Laufs U, Baumer AT, Muller K, Ahlbory K, Linz W, Itter G, Rosen R, Bohm M, Nickenig G. HMG‐CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species. Hypertension 37: 1450‐1457, 2001.
417.	Waypa GB, Marks JD, Mack MM, Boriboun C, Mungai PT, Schumacker PT. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res 91: 719‐726, 2002.
418.	Weaver M, Liu J, Pimentel D, Reddy DJ, Harding P, Peterson EL, Pagano PJ. Adventitial delivery of dominant‐negative p67phox attenuates neointimal hyperplasia of the rat carotid artery. Am J Physiol Heart Circ Physiol 290: H1933‐H1941, 2006.
419.	Wei EP, Christman CW, Kontos HA, Povlishock JT. Effects of oxygen radicals on cerebral arterioles. Am J Phys 248: H157‐H162, 1985.
420.	Wei EP, Kontos HA. H2O2 and endothelium‐dependent cerebral arteriolar dilation. Implications for the identity of endothelium‐derived relaxing factor generated by acetylcholine. Hypertension 16: 162‐169, 1990.
421.	Wei EP, Kontos HA, Beckman JS. Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. Am J Phys 271: H1262‐H1266, 1996.
422.	Wei Y, Sowers JR, Nistala R, Gong H, Uptergrove GM, Clark SE, Morris EM, Szary N, Manrique C, Stump CS. Angiotensin II‐induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells. J Biol Chem 281: 35137‐35146, 2006.
423.	Weller RB. Sunlight has cardiovascular benefits independently of vitamin D. Blood Purif 41: 130‐134, 2016.
424.	Wesson DE, Elliott SJ. The H2O2‐generating enzyme, xanthine oxidase, decreases luminal Ca2+ content of the IP3‐sensitive Ca2+ store in vascular endothelial cells. Microcirculation 2: 195‐203, 1995.
425.	White WB. Cardiovascular effects of the cyclooxygenase inhibitors. Hypertension 49: 408‐418, 2007.
426.	Williams C, Wick TM. Endothelial cell‐smooth muscle cell co‐culture in a perfusion bioreactor system. Ann Biomed Eng 33: 920‐928, 2005.
427.	Wind S, Beuerlein K, Eucker T, Muller H, Scheurer P, Armitage ME, Ho H, Schmidt HH, Wingler K. Comparative pharmacology of chemically distinct NADPH oxidase inhibitors. Br J Pharmacol 161: 885‐898, 2010.
428.	Xiang L, Dearman J, Abram SR, Carter C, Hester RL. Insulin resistance and impaired functional vasodilation in obese Zucker rats. Am J Physiol Heart Circ Physiol 294: H1658‐H1666, 2008.
429.	Xie L, Zeng D, Zhang H, Sun D, Pang X, Guan Q. Involvement of Rho‐kinase in collar‐induced vasoconstriction and vascular hypersensitivity to serotonin in rat carotid. Int J Cardiol 148: 168‐173, 2011.
430.	Yada T, Shimokawa H, Morikawa K, Takaki A, Shinozaki Y, Mori H, Goto M, Ogasawara Y, Kajiya F. Role of Cu,Zn‐SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo. Am J Physiol Heart Circ Physiol 294: H441‐H448, 2008.
431.	Yamagishi S, Nakamura K, Matsui T, Inagaki Y, Takenaka K, Jinnouchi Y, Yoshida Y, Matsuura T, Narama I, Motomiya Y, Takeuchi M, Inoue H, Yoshimura A, Bucala R, Imaizumi T. Pigment epithelium‐derived factor inhibits advanced glycation end product‐induced retinal vascular hyperpermeability by blocking reactive oxygen species‐mediated vascular endothelial growth factor expression. J Biol Chem 281: 20213‐20220, 2006.
432.	Yang D, Feletou M, Boulanger CM, Wu HF, Levens N, Zhang JN, Vanhoutte PM. Oxygen‐derived free radicals mediate endothelium‐dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats. Br J Pharmacol 136: 104‐110, 2002.
433.	Yasuda M, Ohzeki Y, Shimizu S, Naito S, Ohtsuru A, Yamamoto T, Kuroiwa Y. Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS‐1 in endothelial cells. Life Sci 64: 249‐258, 1999.
434.	Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P, Investigators HOPES. Vitamin E supplementation and cardiovascular events in high‐risk patients. N Engl J Med 342: 154‐160, 2000.
435.	Zhang C, Hein TW, Wang W, Ren Y, Shipley RD, Kuo L. Activation of JNK and xanthine oxidase by TNF‐alpha impairs nitric oxide‐mediated dilation of coronary arterioles. J Mol Cell Cardiol 40: 247‐257, 2006.
436.	Zhang C, Rogers PA, Merkus D, Muller‐Delp JM, Tiefenbacher CP, Potter B, Knudson JD, Rocic P, Chilian WM. Regulation of coronary microvascular resistance in health and disease. In: Comprehensive Physiology. John Wiley & Sons, Inc., 2011.
437.	Zhang M, Brewer AC, Schroder K, Santos CX, Grieve DJ, Wang M, Anilkumar N, Yu B, Dong X, Walker SJ, Brandes RP, Shah AM. NADPH oxidase‐4 mediates protection against chronic load‐induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci U S A 107: 18121‐18126, 2010.
438.	Zhang M, Shah AM. ROS signalling between endothelial cells and cardiac cells. Cardiovasc Res 102: 249‐257, 2014.
439.	Zhang X, Staimer N, Tjoa T, Gillen DL, Schauer JJ, Shafer MM, Hasheminassab S, Pakbin P, Longhurst J, Sioutas C, Delfino RJ. Associations between microvascular function and short‐term exposure to traffic‐related air pollution and particulate matter oxidative potential. Environ Health 15: 81, 2016.
440.	Zhang Y, Oltman CL, Lu T, Lee HC, Dellsperger KC, VanRollins M. EET homologs potently dilate coronary microvessels and activate BK(Ca) channels. Am J Physiol Heart Circ Physiol 280: H2430‐H2440, 2001.
441.	Zhao X, Alexander JS, Zhang S, Zhu Y, Sieber NJ, Aw TY, Carden DL. Redox regulation of endothelial barrier integrity. Am J Physiol Lung Cell Mol Physiol 281: L879‐L886, 2001.
442.	Zhou X, Bohlen HG, Miller SJ, Unthank JL. NAD(P)H oxidase‐derived peroxide mediates elevated basal and impaired flow‐induced NO production in SHR mesenteric arteries in vivo. Am J Physiol Heart Circ Physiol 295: H1008‐H1016, 2008.
443.	Zhu XY, Daghini E, Chade AR, Rodriguez‐Porcel M, Napoli C, Lerman A, Lerman LO. Role of oxidative stress in remodeling of the myocardial microcirculation in hypertension. Arterioscler Thromb Vasc Biol 26: 1746‐1752, 2006.
444.	Ziche M, Morbidelli L, Masini E, Granger H, Geppetti P, Ledda F. Nitric oxide promotes DNA synthesis and cyclic GMP formation in endothelial cells from postcapillary venules. Biochem Biophys Res Commun 192: 1198‐1203, 1993.
445.	Zielonka J, Sikora A, Adamus J, Kalyanaraman B. Detection and differentiation between peroxynitrite and hydroperoxides using mitochondria‐targeted arylboronic acid. Methods Mol Biol 1264: 171‐181, 2015.
446.	Zinkevich NS, Gutterman DD. ROS‐induced ROS release in vascular biology: Redox‐redox signaling. Am J Physiol Heart Circ Physiol 301: H647‐H653, 2011.
447.	Zuo L, Chuang CC, Hemmelgarn BT, Best TM. Heart failure with preserved ejection fraction: Defining the function of ROS and NO. J Appl Physiol (1985) 119: 944‐951, 2015.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title:	Redox Regulation of the Microcirculation
* Name:
* E-mail:
* Note:

How to Cite

Andrew O. Kadlec, David D. Gutterman. Redox Regulation of the Microcirculation. Compr Physiol 2019, 10: 229-259. doi: 10.1002/cphy.c180039

Collections

Free Featured Articles