Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Intrinsic Prostaglandin Biosynthesis in Blood Vessels

Philip Needleman, Peter C. Isakson

10.1002/cphy.cp020220

Source: Supplement 7: Handbook of Physiology, The Cardiovascular System, Vascular Smooth Muscle

Originally published: 1980

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Prostaglandin Synthesis and General Properties
1.1 Biosynthesis of Prostaglandins
1.2 Effects of Exogenous Prostaglandins on Vascular Smooth Muscle
1.3 Summary
2 Prostaglandins and the Mesenteric and Celiac Arteries
2.1 Intrinsic Vascular Synthesis of Prostaglandins
2.2 Influence of Local Vascular Prostaglandins on Neuronal Activity and Blood Vessel Tone
2.3 Differential PG Synthesis in Arteries and Veins
3 Prostaglandin Biosynthesis in the Ductus Arteriosus
4 Human Umbilical Artery
4.1 Intrinsic Prostaglandin Biosynthesis
4.2 Prostaglandin Synthesis in Blood Vessel Tissue Culture
5 Coronary Arteries
5.1 Contribution of Intrinsic Prostaglandins to Coronary Tone
5.2 Paradoxical Endogenous Synthesis of a Coronary Dilating Substance from Arachidonate
5.3 Effect of Prostaglandin Endoperoxides on Bovine Coronary Arteries
5.4 Novel Metabolic Arachidonate Pathway that Generates a Potent Endogenous Vasodilator
6 Prostacyclin
6.1 Arterial Synthesis of a Novel Prostaglandin that Inhibits Platelet Aggregation
6.2 Inhibition of the Vascular Synthesis of the Novel Prostaglandin
6.3 Intrinsic Vascular Synthesis of a Prostaglandin Vasodilator in Mesenteric, Celiac, and Coronary Arteries
6.4 Chemical Identification of Prostacyclin
6.5 Prostacyclin and Thromboxane A2 Characterization Criteria
7 Pathophysiological Significance of Vascular Prostacyclin Synthesis and its Pharmacological Modification
Figure 1. Figure 1.

Schematic pathway and structures for the liberation and oxidation of arachidonic acid.
Figure 2. Figure 2.

Schematic pathway for the conversion of endoperoxides to various prostaglandin products. Side chains are deleted from some of the products of the endoperoxide for the sake of illustration. PG, prostaglandin; TA2, thromboxane A2; TB2, thromboxane B2.
Figure 3. Figure 3.

Responses of strips of vascular smooth muscle from various sources to several concentrations of the prostaglandins. Responses are expressed as a percentage of the contractile response to 50 mM KCl. Aortic and coronary arterial strips are contracted by the prostaglandins. But smooth muscle cells from small muscular, mesenteric, and renal arteries show a biphasic dose‐response relationship with the prostaglandins: the cells relax when exposed to low concentrations and contract when exposed to higher concentrations.

From Strong and Bohr 127
Figure 4. Figure 4.

Differential bioassay of aorta‐contracting substances in rabbit. PGG2 (200 ng) was added to 500 μl of TRIS buffer (50 mM, pH 7.8) at 0°C, and a 50 μl sample (equivalent to 20 ng) was tested. Immediately after testing, horse platelet microsomes were added to the PGG2 solution, and 50 μl of the solution was tested 2 min later.

From Needleman et al. 105
Figure 5. Figure 5.

Comparative potency of prostaglandin endoperoxides and thromboxanes. Values represent the mean ± SE, and number in parentheses represents number of aorta strips tested. Thromboxanes (i.e., thromboxane A2 = PGH2 + platelets, and thromboxane A3 = PGH3 + platelets) were generated by incubating the endoperoxides with 15 μl of human platelet microsomes before being tested on the aortic strip for 2 min at 0°C.

From Needleman et al. 104. Copyright 1976 by the American Association for the Advancement of Science
Figure 6. Figure 6.

A: response of assay organs and perfused rabbit mesentery to angiotensin II (AII) and bradykinin (BK). B: the influence of Sar1, Ile8‐AII and indomethacin. Two assay organs selected for their sensitivity to prostaglandins were recorded simultaneously. Injections of substances in amounts indicated (all ng) were made directly (DIR) into Kreb's solution that was supervising assay organs or into fluid just before it entered mesentery (TM). AII applied directly to the assay organs had no effect on the isolated chick rectum but contracted the rat stomach strip. The specific antagonist Sar1, Ile8‐AII was infused across the assay tissues, and it blocked the direct effect of AII on the rat stomach strip, enhancing the strip's specificity for prostaglandinlike substances.

Prom Blumberg, Needleman, et al. 14
Figure 7. Figure 7.

Schematic representation of hormonal interactions in blood vessels. AI, angiotensin I; AII, angiotensin II; BK, bradykinin; PG, prostaglandin; Sar1, Ile8‐AII, a receptor blocker; SQ‐20881, a nonapeptide that inhibits the conversion of AI to AII and that blocks the destruction of bradykinin.
Figure 8. Figure 8.

Actions and interactions of prostaglandin synthesis inhibitors on bovine coronary arterial strips. A: strip exposed to aspirin (ASA) (1 × 10−5 g/ml) and to indomethacin (INDO) (1 × 10−5 g/ml). B: strip exposed to indomethacin followed by aspirin. C: strip treated with 5,8,11,14‐eicosatetraynoic acid (ETA) (1 × 10−5 g/ml) for 15 min, and the muscle chamber washed at arrow, followed by aspirin and indomethacin.

From Kalsner 72
Figure 9. Figure 9.

Responses of bovine coronary arterial strips to decreased oxygen and to sodium nitrite. Upper curve for strip under the standard PO2 of 515 mmHg exposed to a PO2 of 53 mmHg (dot) and subsequently returned to the standard 515 mmHg (dot), followed by NaNO2 (NO2) (1 × 10−3 g/ml). Lower curve for strip (taken from the same vessel as in upper curve) pretreated with aspirin (1 × 10−5 g/ml) under the standard PO2 of 515 mmHg and then treated as the strip in upper curve.

From Kalsner 73
Figure 10. Figure 10.

Effect of arachidonate (AA) on the bovine coronary artery. Arrows at the bottom indicate addition of the drugs to the media. A: strip was partially contracted with PGE2 (1 μg/ml) and a steady‐state contractile response was reached. Dose‐dependent relaxation responses were obtained by cumulative additions of arachidonate. Addition of 10 μg/ml indomethacin (INDO) caused contraction. B: same strip was washed for 11/2 h and indomethacin (10 μg/ml) was re‐added to the media. Strip was contracted by PGE2, (1 μg/ml) and arachidonate added at this point was without effect.

From Kulkarni, Roberts, and Needleman 76
Figure 11. Figure 11.

Representative tracings showing the pattern of tension changes in pig coronary arteries (blocked against 5‐hydroxytryptamine) in response to the addition of four substances. A: washed platelets stimulated with thrombin for 30 s; B: 225 nM PGE2; C: 255 nM PGH2; and D: platelet particles plus 225 nM PGH2 (i.e., thromboxane A2). All tracings have the same tension scale.

From Ellis et al. 31. Copyright 1976 by the American Association for the Advancement of Science
Figure 12. Figure 12.

Comparative arterial vascular responsiveness to the endoperoxide PGH2. In experiments designed to simultaneously compare the endoperoxide response in blood vessels removed from various species, a superfusion cascade was used. Spirals of blood vessels were continuously perfused (10 ml/min) with Krebs‐Henseleit solution (95% O2 + 5% CO2) that contained a mixture of antagonists that rendered the tissues insensitive to catecholamines, histamine, acetylcholine, and serotonin.

From Needleman et al. 101. Copyright 1977 by the American Association for the Advancement of Science
Figure 13. Figure 13.

Dose‐dependent and species‐dependent contraction or relaxation of coronary arterial strips to exogenous prostaglandin endoperoxides and to the primary PGEs (series 1, 2, and 3).

From Needleman et al. 101
Figure 14. Figure 14.

Coronary relaxant effect of PGH2. Upper panel illustrates a typical recording of the coronary relaxation produced either by direct PGH2 addition to a superfused (10 ml/min of Krebs‐Henseleit medium) bovine coronary arterial strip or by addition of the reaction mixture with the same amount of PGH2 incubated with bovine coronary arterial microsomes (2 min at 22°C). Microsomes themselves have no direct effect. Lower panel presents a dose‐response curve comparing the potency of PGH2 alone versus the so‐called activated product produced by the coronary microsomes.

From Raz, Needleman, et al. 119
Figure 15. Figure 15.

Comparison of inhibition of aggregation by PGX and PGE1. PGX in concentrations (per ml) of 0.5 or 0.25 ng incubated for 1 min in platelet‐rich plasma before the addition of arachidonic acid (AA) (0.9 mM) resulted in dose‐dependent inhibition of the resulting aggregation. PGE1 (20 or 10 ng/ml) also inhibited aggregation but was about 40 times less potent than PGX.

From Moncada et al. 94
Figure 16. Figure 16.

Effect of 15‐hydroperoxy arachidonic acid (15‐HPAA) at 1 μg/ml on the responses of strips of rabbit aorta and rabbit celiac and mesenteric arteries to PGG2 and PGX (prostacyclin). PGG2 (100 ng) contracted the rabbit aorta and caused a small contraction followed by a longer lasting relaxation of the celiac and mesenteric arteries. PGX, formed by incubating PGG2 (100 ng) with 250 μg pig aortic microsomes (AM), did not contract rabbit aorta but relaxed the celiac and mesenteric arteries, because PGX is more potent than the parent endoperoxide. A 5‐min infusion of 15‐HPAA (1 μg/ml) caused contraction of all tissues (not shown). PGG2 (100 ng) gave a much greater contraction of rabbit aorta 1 h later, and also contracted celiac and mesenteric arteries. Activity of PGX was not significantly altered after the 15‐HPAA infusion.

From Bunting et al. 18
Figure 17. Figure 17.

Schematic representation of the pathways of prostaglandin metabolism. Primary substrates and products are indicated in the boxes; enzymes are presented in slanted lower case type; and the enzymatic inhibitors and their currently known site of action are indicated by X.
Figure 18. Figure 18.

Interaction of platelets with normal vascular wall. Platelets, attempting to stick, generate endoperoxides that are then converted by the vessel enzyme into prostacyclin (PGX).

From Moncada and Vane 97
Figure 19. Figure 19.

Vascular damage uncovers proaggregating material from the vessel wall. Platelets interact with this proaggregating material and release thromboxane A2 (TXA2).

From Moncada and Vane 97


Figure 1.

Schematic pathway and structures for the liberation and oxidation of arachidonic acid.



Figure 2.

Schematic pathway for the conversion of endoperoxides to various prostaglandin products. Side chains are deleted from some of the products of the endoperoxide for the sake of illustration. PG, prostaglandin; TA2, thromboxane A2; TB2, thromboxane B2.



Figure 3.

Responses of strips of vascular smooth muscle from various sources to several concentrations of the prostaglandins. Responses are expressed as a percentage of the contractile response to 50 mM KCl. Aortic and coronary arterial strips are contracted by the prostaglandins. But smooth muscle cells from small muscular, mesenteric, and renal arteries show a biphasic dose‐response relationship with the prostaglandins: the cells relax when exposed to low concentrations and contract when exposed to higher concentrations.

From Strong and Bohr 127


Figure 4.

Differential bioassay of aorta‐contracting substances in rabbit. PGG2 (200 ng) was added to 500 μl of TRIS buffer (50 mM, pH 7.8) at 0°C, and a 50 μl sample (equivalent to 20 ng) was tested. Immediately after testing, horse platelet microsomes were added to the PGG2 solution, and 50 μl of the solution was tested 2 min later.

From Needleman et al. 105


Figure 5.

Comparative potency of prostaglandin endoperoxides and thromboxanes. Values represent the mean ± SE, and number in parentheses represents number of aorta strips tested. Thromboxanes (i.e., thromboxane A2 = PGH2 + platelets, and thromboxane A3 = PGH3 + platelets) were generated by incubating the endoperoxides with 15 μl of human platelet microsomes before being tested on the aortic strip for 2 min at 0°C.

From Needleman et al. 104. Copyright 1976 by the American Association for the Advancement of Science


Figure 6.

A: response of assay organs and perfused rabbit mesentery to angiotensin II (AII) and bradykinin (BK). B: the influence of Sar1, Ile8‐AII and indomethacin. Two assay organs selected for their sensitivity to prostaglandins were recorded simultaneously. Injections of substances in amounts indicated (all ng) were made directly (DIR) into Kreb's solution that was supervising assay organs or into fluid just before it entered mesentery (TM). AII applied directly to the assay organs had no effect on the isolated chick rectum but contracted the rat stomach strip. The specific antagonist Sar1, Ile8‐AII was infused across the assay tissues, and it blocked the direct effect of AII on the rat stomach strip, enhancing the strip's specificity for prostaglandinlike substances.

Prom Blumberg, Needleman, et al. 14


Figure 7.

Schematic representation of hormonal interactions in blood vessels. AI, angiotensin I; AII, angiotensin II; BK, bradykinin; PG, prostaglandin; Sar1, Ile8‐AII, a receptor blocker; SQ‐20881, a nonapeptide that inhibits the conversion of AI to AII and that blocks the destruction of bradykinin.



Figure 8.

Actions and interactions of prostaglandin synthesis inhibitors on bovine coronary arterial strips. A: strip exposed to aspirin (ASA) (1 × 10−5 g/ml) and to indomethacin (INDO) (1 × 10−5 g/ml). B: strip exposed to indomethacin followed by aspirin. C: strip treated with 5,8,11,14‐eicosatetraynoic acid (ETA) (1 × 10−5 g/ml) for 15 min, and the muscle chamber washed at arrow, followed by aspirin and indomethacin.

From Kalsner 72


Figure 9.

Responses of bovine coronary arterial strips to decreased oxygen and to sodium nitrite. Upper curve for strip under the standard PO2 of 515 mmHg exposed to a PO2 of 53 mmHg (dot) and subsequently returned to the standard 515 mmHg (dot), followed by NaNO2 (NO2) (1 × 10−3 g/ml). Lower curve for strip (taken from the same vessel as in upper curve) pretreated with aspirin (1 × 10−5 g/ml) under the standard PO2 of 515 mmHg and then treated as the strip in upper curve.

From Kalsner 73


Figure 10.

Effect of arachidonate (AA) on the bovine coronary artery. Arrows at the bottom indicate addition of the drugs to the media. A: strip was partially contracted with PGE2 (1 μg/ml) and a steady‐state contractile response was reached. Dose‐dependent relaxation responses were obtained by cumulative additions of arachidonate. Addition of 10 μg/ml indomethacin (INDO) caused contraction. B: same strip was washed for 11/2 h and indomethacin (10 μg/ml) was re‐added to the media. Strip was contracted by PGE2, (1 μg/ml) and arachidonate added at this point was without effect.

From Kulkarni, Roberts, and Needleman 76


Figure 11.

Representative tracings showing the pattern of tension changes in pig coronary arteries (blocked against 5‐hydroxytryptamine) in response to the addition of four substances. A: washed platelets stimulated with thrombin for 30 s; B: 225 nM PGE2; C: 255 nM PGH2; and D: platelet particles plus 225 nM PGH2 (i.e., thromboxane A2). All tracings have the same tension scale.

From Ellis et al. 31. Copyright 1976 by the American Association for the Advancement of Science


Figure 12.

Comparative arterial vascular responsiveness to the endoperoxide PGH2. In experiments designed to simultaneously compare the endoperoxide response in blood vessels removed from various species, a superfusion cascade was used. Spirals of blood vessels were continuously perfused (10 ml/min) with Krebs‐Henseleit solution (95% O2 + 5% CO2) that contained a mixture of antagonists that rendered the tissues insensitive to catecholamines, histamine, acetylcholine, and serotonin.

From Needleman et al. 101. Copyright 1977 by the American Association for the Advancement of Science


Figure 13.

Dose‐dependent and species‐dependent contraction or relaxation of coronary arterial strips to exogenous prostaglandin endoperoxides and to the primary PGEs (series 1, 2, and 3).

From Needleman et al. 101


Figure 14.

Coronary relaxant effect of PGH2. Upper panel illustrates a typical recording of the coronary relaxation produced either by direct PGH2 addition to a superfused (10 ml/min of Krebs‐Henseleit medium) bovine coronary arterial strip or by addition of the reaction mixture with the same amount of PGH2 incubated with bovine coronary arterial microsomes (2 min at 22°C). Microsomes themselves have no direct effect. Lower panel presents a dose‐response curve comparing the potency of PGH2 alone versus the so‐called activated product produced by the coronary microsomes.

From Raz, Needleman, et al. 119


Figure 15.

Comparison of inhibition of aggregation by PGX and PGE1. PGX in concentrations (per ml) of 0.5 or 0.25 ng incubated for 1 min in platelet‐rich plasma before the addition of arachidonic acid (AA) (0.9 mM) resulted in dose‐dependent inhibition of the resulting aggregation. PGE1 (20 or 10 ng/ml) also inhibited aggregation but was about 40 times less potent than PGX.

From Moncada et al. 94


Figure 16.

Effect of 15‐hydroperoxy arachidonic acid (15‐HPAA) at 1 μg/ml on the responses of strips of rabbit aorta and rabbit celiac and mesenteric arteries to PGG2 and PGX (prostacyclin). PGG2 (100 ng) contracted the rabbit aorta and caused a small contraction followed by a longer lasting relaxation of the celiac and mesenteric arteries. PGX, formed by incubating PGG2 (100 ng) with 250 μg pig aortic microsomes (AM), did not contract rabbit aorta but relaxed the celiac and mesenteric arteries, because PGX is more potent than the parent endoperoxide. A 5‐min infusion of 15‐HPAA (1 μg/ml) caused contraction of all tissues (not shown). PGG2 (100 ng) gave a much greater contraction of rabbit aorta 1 h later, and also contracted celiac and mesenteric arteries. Activity of PGX was not significantly altered after the 15‐HPAA infusion.

From Bunting et al. 18


Figure 17.

Schematic representation of the pathways of prostaglandin metabolism. Primary substrates and products are indicated in the boxes; enzymes are presented in slanted lower case type; and the enzymatic inhibitors and their currently known site of action are indicated by X.



Figure 18.

Interaction of platelets with normal vascular wall. Platelets, attempting to stick, generate endoperoxides that are then converted by the vessel enzyme into prostacyclin (PGX).

From Moncada and Vane 97


Figure 19.

Vascular damage uncovers proaggregating material from the vessel wall. Platelets interact with this proaggregating material and release thromboxane A2 (TXA2).

From Moncada and Vane 97
References
 1. Aboulafia, J., G. B. Mendis, M. E. Miyamoto, A. C. M. Paiva, and T. B. Paiva. Effect of indomethacin and prostaglandin on the smooth muscle contracting activity of angiotensin and other agonists. Brit. J. Pharmacol. 58: 223–228, 1976.
 2. Aiken, J. W. Effects of prostaglandin synthesis inhibitors on angiotensin tachyphylaxis on the isolated coeliac and the mesenteric arteries of the rabbit. Polish J. Pharmacol. Pharm. 26: 217–227, 1974.
 3. Aiken, J. W., and J. R. Vane. Blockade of angiotensin‐induced prostaglandin release from dog kidney by indomethacin. J. Pharmacol. Exptl. Therap. 184: 678–687, 1973.
 4. Alexander, R. W., and M. A. Gimbrone, Jr. Stimulation of prostaglandin E synthesis in cultured human umbilical vein smooth muscle cells. Proc. Natl. Acad. Sci. US 73: 1617–1620, 1976.
 5. Allen, G. S., C. J. Gross, L. A. French, and S. N. Chou. Cerebral arterial spasm. 5. In vitro contractile activity of vasoactive agents including CSF on human basilar and anterior cerebral arteries. J. Neurosurg. 44: 594–600, 1976.
 6. Allen, G. S., L. M. Henderson, S. N. Chou, and L. A. French. Cerebral arterial spasm. 1. In vitro contractile activity of vasoactive agents on canine basilar and middle cerebral arteries. J. Neurosurg. 40: 433–441, 1974.
 7. Altura, B. M., D. Malaviya, C. F. Reich, and L. R. Orkin. Effects of vasoactive agents on isolated human umbilical arteries and veins. Am. J. Physiol. 222: 345–355, 1972.
 8. Altura, B. M., and B. T. Altura. Vascular smooth muscle and prostaglandins. Federation Proc. 35: 2360–2366, 1976.
 9. Angaard, E., and S. Bergstrom. Biological effects of an unsaturated trihydroxy acid (PGF2α) from normal swine lung. Acta Physiol. Scand. 58: 1–12, 1963.
 10. Arcilla, R. A., O. G. Thilenius, and K. Ranniger. Congestive heart failure from suspected ductal closure in utero. J. Pediat. 75: 74–78, 1969.
 11. Bergstrom, S., L. A. Carlson, and J. R. Weeks. The prostaglandins: A family of biologically active lipids. Pharmacol. Rev. 20: 1–48, 1968.
 12. Bergstrom, S., H. Danielsson, and B. Samuelsson. The enzymatic formation of prostaglandin E2 from arachidonic acid. Biochim. Biophys. Acta 90: 207–210, 1964.
 13. Bergstrom, S. R., R. Eliasson, U. A. Von Euler, and J. Sjovall. Some biological effects of two crystalline prostaglandin factors. Acta Physiol. Scand. 45: 133–144, 1959.
 14. Blumberg, A. L., S. E. Denny, G. R. Marshall, and P. Needleman. Blood vessel‐hormone interactions: angiotensin, bradykinin and prostaglandins. Am. J. Physiol. 232: H305–H310, 1977 or
 15. Am. J. Physiol.: Heart Circ. Physiol. 1: H305–H310, 1977.
 16. Blumberg, A., S. Denny, K. Nishikawa, E. Pure, G. R. Marshall, and P. Needleman. Angiotensin‐III‐induced prostaglandin release. Prostaglandins 11: 195–197, 1976.
 17. Blumberg, A. L., K. Nishikawa, S. E. Denny, G. R. Marshall, and P. Needleman. Angiotensin (A‐I, AII, AIII) receptor characterization: correlation of prostaglandin release with peptide degradation. Circulation Res. 41: 154–158, 1977.
 18. Bor, I., and W. G. Guntheroth. In vitro response to oxygen of human umbilical arteries and of animal ductus arteriosus. Can. J. Physiol. Pharmacol. 48: 500–502, 1970.
 19. Bunting, S., R. Gryglewski, S. Moncada, and J. R. Vane. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins 12: 897–913, 1976.
 20. Chandler, J. T., and C. G. Strong. The actions of prostaglandin E1 on isolated rabbit aorta. Arch. Intern. Pharmacodyn. 197: 123–131, 1972.
 21. Christ, E. J., and D. A. Van Dorp. Comparative aspects of prostaglandin biosynthesis in animal tissues. International Workshop on Prostaglandins, edited by S. Bergstroem. New York: Pergamon, 1972, p. 35–38. (Advances in the Biosciences, edited by G. Raspé and S. Bernhard, vol. 9.)
 22. Clyman, R. I., A. S. Blacksin, V. C. Manganiello, and M. Vaughan. Oxygen and cyclic nucleotides in human umbilical artery. Proc. Natl. Acad. Sci. US 72: 3883–3887, 1975.
 23. Clyman, R. I., M. A. Heymann, and A. M. Rudolph. Ductus arteriosis responses to prostaglandin E1 at high and low oxygen concentrations. Prostaglandins 13: 219–223, 1977.
 24. Clyman, R. I., J. A. Sandler, V. C. Manganiello, and M. Vaughan. Guanosine 3′,5′‐monophosphate content of human umbilical artery. Possible role in perinatal arterial potency and closure. J. Clin. Invest. 55: 1020–1025, 1975.
 25. Coceani, F., P. M. Olley, and E. Bodach. Prostaglandins: A possible regulator of muscle tone in the ductus arteriosus. In: Advances in Prostaglandin and Thromboxane Research, edited by B. Samuelsson and R. Paoletti. New York: Raven, 1976, vol. II, p. 417–424.
 26. Cohen, M. M., C. V. Greenway, I. R. Innes, G. E. Loster, V. S. Murthy, and G. D. Scott. Further observations on mesenteric vasoconstriction, survival, and the clotting defect after endotoxin administration. Brit. J. Pharmacol. 48: 555–569, 1973.
 27. DuCharme, D. W., J. R. Weeks, and R. G. Montgomery. Studies on the mechanism of the hypertensive effect of prostaglandin F2α. J. Pharmacol. Exptl. Therap. 160: 1–10, 1968.
 28. Dunham, E. W., M. K. Haddox, and N. D. Goldberg. Alteration of vein cyclic 3′,5′ nucleotide concentrations during changes in contractility. Proc. Natl. Acad. Sci. US 71: 815–819, 1974.
 29. Dusting, G. J., S. Moncada, and J. R. Vane. Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachidonic acid. Prostaglandins 13: 3–16, 1977.
 30. Dyer, D. C. Comparison of the constricting actions produced by serotonin and prostaglandins on isolated sheep umbilical arteries and veins. Gynecol. Invest. 1: 204–209, 1970.
 31. Elliott, R. B., M. B. Starling, and J. M. Neutze. Medical manipulation of the ductus arteriosus. Lancet 1: 140–142, 1975.
 32. Ellis, E. F., O. Olez, A. S. Nies, G. R. Wilkinson, and J. A. Oates. Contraction of coronary arterial smooth muscle by substances released from platelets. Circulation 52: 496, 1975.
 33. Ellis, E. F., O. Oelz, L. J. Roberts, N. A. Payne, B. J. Sweetman, A. S. Nies, and J. A. Oates. Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2. Science 193: 1135–1137, 1976.
 34. Etherington, L. G., J. Stoff, T. Hughes, and K. L. Melmon. Constriction of human umbilical arteries interaction between oxygen and bradykinin. Circulation Res. 22: 747–752, 1968.
 35. Ferreira, S. H., and J. R. Vane. Prostaglandins: their disappearance from and release into the circulation. Nature 216: 868–873, 1967.
 36. Folkow, B., B. Johnson, and S. Mellander. A comparison of the effects of noradrenaline and angiotensin on the resistance and the capacitance vessels in the cat. Acta Physiol. Scand. 175: 50–58, 1960.
 37. Friedman, W. F., M. J. Hirschklau, M. P. Printz, P. T. Pitlick, and S. E. Kirkpatrick. Pharmacologic closure of patent ductus arteriosus in the premature infant. New Engl. J. Med. 295: 526–529, 1976.
 38. Ganten, D., K. Hayduk, H. J. Brecht, R. Boucher, and J. Genest. Evidence of renin release or production in splanchnic territory. Nature 226: 551–552, 1970.
 39. Gimbrone, M. A.Jr., and R. W. Alexander. Angiotensin II stimulation of prostaglandin production in cultured human vascular endothelium. Science 189: 219–220, 1975.
 40. Goldberg, M. R., P. D. Joiner, S. Greenberg, A. L. Hyman, and P. J. Kadowitz. Effects of indomethacin on venoconstrictor responses to bradykinin and norepinephrine. Prostaglandins 9: 385–390, 1975.
 41. Goldblatt, M. W. A depressor substance in seminal fluid. J. Soc. Chem. Ind. London 52: 1056–1057, 1933.
 42. Goldblatt, M. W. Properties of human seminal plasma. J. Physiol. London 84: 208–218, 1935.
 43. Goldyne, M. E., and R. K. Winkelmann. In vitro effects of prostaglandin E2 on cutaneous vascular smooth muscle in the dog and in man. J. Invest. Dermatol. 60: 258–262, 1973.
 44. Greenberg, R. A., and H. V. Sparks. Prostaglandins and consecutive vascular segments of the canine hindlimb. Am. J. Physiol. 216: 567–571, 1969.
 45. Greenberg, S., P. J. Kadowitz, F. P. J. Diecke, and J. P. Long. Effect of prostaglandin F2α on responses of vascular smooth muscle to serotonin, angiotensin and epinephrine. Arch. Intern Pharmacodyn. 206: 5–18, 1973.
 46. Greenberg, S., P. J. Kadowitz, J. P. Long, and W. R. Wilson. Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle. Circulation Res. 39: 66–76, 1976.
 47. Greenberg, S., and J. P. Long. Enhancement of vascular smooth muscle responses to vasoactive stimuli by prostaglandin E1 and E2. Arch. Intern. Pharmacodyn. 206: 94–104, 1973.
 48. Grodzinska, L., B. Panczenko, and R. J. Gryglewski. Release of prostaglandin‐E‐like material from perfused mesenteric blood vessels of rabbits. J. Pharm. Pharmacol. 28: 40–43, 1976.
 49. Gryglewski, R. J., S. Bunting, S. Moncada, R. J. Flower, and J. R. Vane. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685–713, 1976.
 50. Gryglewski, R. J., and R. Korbut. Prostaglandin feedback mechanism limits vasoconstrictor action of norepinephrine in perfused rabbit ear. Experientia 31: 89–91, 1975.
 51. Gryglewski, R. J., and A. Ocetkiewicz. A release of prostaglandins may be responsible for acute tolerance to norepinephrine infusions. Prostaglandins 8: 31–42, 1974.
 52. Gryglewski, R. J., B. Panczenko, R. Korbut, L. Grodzinska, and A. Ocetkiewicz. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins 10: 343–354, 1975.
 53. Hamberg, M., P. Hedqvist, K. Strandberg, J. Svensson, and B. Samuelsson. Prostaglandin endoperoxides. IV. Effects on smooth muscle. Life Sci. 16: 451–462, 1975.
 54. Hamberg, M., P. Hedqvist, K. Strandberg, J. Svensson, and B. Samuelsson. Prostaglandin endoperoxides: a new concept concerning the mode of action and release of prostaglandins. Proc. Natl. Acad. Sci. US 71: 3824–3828, 1975.
 55. Hamberg, M., and B. Samuelsson. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc. Natl. Acad. Sci. US 70: 899–903, 1973.
 56. Hamberg, M., and B. Samuelsson. Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung. Biochem. Biophys. Res. Common. 61: 942–949, 1974.
 57. Hamberg, M., J. Svensson, and B. Samuelsson. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. US 72: 2994–2998, 1975.
 58. Hamberg, M., J. Svensson, T. Wakabayashi, and B. Samuelsson. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc. Natl. Acad. Sci. US 71: 345–349, 1974.
 59. Hellstrom, H. R. Vasospasm in ischemic heart disease–a hypothesis. Perspectives Biol. Med. 16: 427–440, 1973.
 60. Heymann, M. A., and A. M. Rudolph. Control of the ductus arteriosus. Physiol. Rev. 55: 62–78, 1975.
 61. Heymann, M. A., and A. M. Rudolph. Effects of acetylsalicylic acid on the ductus arteriosus and circulation in fetal lambs in utero. Circulation Res. 38: 418–422, 1976.
 62. Heymann, M. A., A. M. Rudolph, and N. H. Silverman. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. New Engl. J. Med. 295: 530–533, 1976.
 63. Hirsch, L. J., and G. Glick. Mesenteric circulation in cardiogenic shock with and without alpha‐receptor blockade. Am. J. Physiol. 225: 356–359, 1973.
 64. Horrobin, D. F., M. S. Manku, R. Karmali, B. A. Nassar, and P. A. Davies. Aspirin, indomethacin, catecholamine, and prostaglandin interactions on rat arterioles and rabbit hearts. Nature 250: 425–426, 1974.
 65. Isakson, P. C., A. Raz, S. E. Denny, E. Pure, and P. Needleman. A novel prostaglandin is the major product of arachidonic acid metabolism in rabbit heart. Proc. Natl. Acad. Sci. US 74: 101–105, 1977.
 66. Isakson, P. C., A. Raz, and P. Needleman. Selective incorporation of 14C‐arachidonic acid into the phospholipids of intact tissues and subsequent metabolism to 14‐prostaglandins. Prostaglandins 12: 739–748, 1976.
 67. Isakson, P. C., F. Shofer, R. C. McKnight, R. A. Feldhaus, A. Raz, and P. Needleman. Prostaglandins and renin‐angiotensin in systemic canine endotoxemia. J. Pharmacol. Exptl. Therap. 200: 614–622, 1977.
 68. Jackson, H. R., S. M. Johnson, K. H. Ng, W. Pye, and R. C. Hall. The effect of acetylsalicylic acid on the response of the cardiovascular system to catecholamines. European J. Pharmacol. 28: 119–124, 1974.
 69. Johnson, R. A., D. R. Morton, J. H. Kinner, R. R. Gorman, J. C. McGuire, F. F. Sun, N. Whittaker, S. Bunting, J. Salmon, S. Moncada, and J. R. Vane. The chemical structure of prostaglandin X (Prostacyclin). Prostaglandins 12: 915–928, 1976.
 70. Jonsson, C. E., T. Tuvemo, and M. Hamberg. Prostaglandin biosynthesis in the human umbilical cord. Biol. Neonatorum 29: 162–170, 1976.
 71. Juan, H., and F. Lembeck. Release of prostaglandins from the isolated perfused rabbit ear by bradykinin and acetylcholine. Agents Actions. In Press.
 72. Kadar, D., and F. A. Sunahara. Inhibition of prostaglandin effects by ouabain in the canine vascular tissue. Can. J. Physiol. Pharmacol. 47: 871–879, 1969.
 73. Kadowitz, P. J., P. D. Joiner, A. L. Hyman, and W. J. George. Influence of prostaglandins E1 and F2α on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels. J. Pharmacol Exptl. Therap. 192: 677–687, 1975.
 74. Kalsner, S. Responses to and termination of action of prostaglandins in vascular tissue of the rabbit. Can. J. Physiol. Pharmacol. 52: 1020–1025, 1974.
 75. Kalsner, S. Endogenous prostaglandin release contributes directly to coronary artery tone. Can. J. Physiol. Pharmacol. 53: 560–565, 1975.
 76. Kalsner, S. Intrinsic prostaglandin release. A mediator of anoxia‐induced relaxation in an isolated coronary artery preparation. Blood Vessels 13: 155–166, 1976.
 77. Karim, S. M. M. The identification of prostaglandins in human umbilical cord. Brit. J. Pharmacol. Chemother. 29: 230–237, 1967.
 78. Khairallah, P. A., I. H. Page, and R. K. Turker. Some properties of prostaglandin E1 action on muscle. Arch. Intern. Pharmacodyn. 169: 328–341, 1967.
 79. Kulkarni, P. S., R. Roberts, and P. Needleman. Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate. Prostaglandins 12: 337–353, 1976.
 80. Lande, I. S. D., R. C. Hall, J. A. Hall, and G. D. Higgins. Prostaglandins, antipyretic analgesics and adrenergic stimuli on the isolated artery. European J. Pharmacol. 30: 319–327, 1975.
 81. Lands, W. E. M., and B. Samuelsson. Phospholipid precursors of prostaglandins. Biochim. Biophys. Acta 164: 426–429, 1968.
 82. Lee, J. B., B. G. Covino, B. H. Takman, and E. R. Smith. Renomedullary vasodepressor substance, medullin: isolation, chemical characterization and physiological properties. Circulation Res. 17: 57–77, 1965.
 83. Lembeck, F., H. Popper, and H. Juan. Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn‐Schmiedebergs Arch. Pharmacol. 294: 69–73, 1976.
 84. Leslie, C. A., and L. Levine. Evidence for the presence of a prostaglandin E2‐9‐keto reductase in the rat organs. Biochem. Biophys. Res. Commun. 52: 717–724, 1973.
 85. Malik, K. U., and A. Nasjletti. Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries. Circulation Res. 38: 26–30, 1976.
 86. Malik, K. U., P. Ryan, and J. C. McGiff. Modification by prostaglandin E1 and E2, indomethacin and arachidonic acid of the vasoconstrictor responses of the isolated perfused rabbit and rat mesenteric arteries of adrenergic stimuli. Circulation Res. 39: 163–168, 1976.
 87. McGiff, J. C., and H. Itskovitz. Prostaglandins and the kidney. Circulation Res. 33: 479–488, 1973.
 88. McGiff, J. C., N. A. Terragno, J. Colina, D. A. Terragno, and A. Nasjletti. Prostaglandins and their relationships to the kallikrein‐kinin systems. In: Chemistry and Biology of the Kallikrein‐Kinin System in Health and Disease, edited by J. J. Pisano. 1974, p. 267.
 89. McGregor, D. D. The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J. Physiol. London 177: 21–30, 1965.
 90. McNeill, J. R. Escape of intestinal resistance vessels to angiotensin II. Can. J. Physiol. Pharmacol. 52: 458–464, 1974.
 91. McNeill, J. R., R. D. Stark, and C. V. Greenway. Intestinal vasoconstriction after hemorrhage: roles of vasopressin and angiotensin. Am. J. Physiol. 219: 1342–1347, 1970.
 92. Mellander, S., and B. Johansson. Control of resistance, exchange and capacitance functions in the peripheral circulation. Pharmacol. Rev. 20: 117–196, 1968.
 93. Messina, E. J., R. Weiner, and G. Kaley. Effects of inhibitors of prostaglandin synthesis on arteriolar responsiveness (Abstract). Federation Proc. 32: 788, 1973.
 94. Messina, E. J., R. Weiner, and G. Kaley. Microcirculatory effects of prostaglandins E1, E2, and A1 in the rat mesentery and cremaster muscle. Microvas. Res. 8: 77–89, 1974.
 95. Messina, E. J., R. Weiner, and G. Kaley. Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat. Circulation Res. 37: 430–437, 1975.
 96. Moncada, S., R. J. Gryglewski, S. Bunting, and J. R. Vane. A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 12: 715–737, 1976.
 97. Moncada, S., R. J. Gryglewski, S. Bunting, and J. R. Vane. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–65, 1976.
 98. Moncada, S., E. A. Higgs, and J. R. Vane. Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet 1: 18–20, 1977.
 99. Moncada, S., P. Needleman, J. R. Vane, and S. Bunting. Prostaglandin endoperoxides and thromboxane generating systems and their selective inhibition. Prostaglandins 12: 323–336, 1976.
 100. Moncada, S., and J. R. Vane. The discovery of prostacyclin (PGX): A fresh insight into arachidonic acid metabolism. In: Biochemical Aspects of Prostaglandins and Thromboxanes, edited by J. Freid and N. Karasch. Santa Monica: Intersci. Prostaglandin Symp., 1977, p. 155–178.
 101. Nakano, J. Cardiovascular actions. In: The Prostaglandins, edited by P. W. Ramwell. New York: Plenum, 1973, p. 239–316.
 102. Needleman, P. The synthesis and function of prostaglandins in the heart. Federation Proc. 35: 2376–2381, 1976.
 103. Needleman, P., S. L. Key, S. E. Denny, P. C. Isakson, and G. R. Marshall. Mechanism and modification of bradykinin‐induced coronary vasodilation. Proc. Natl. Acad. Sci. US 72: 2060–2063, 1975.
 104. Needleman, P., P. S. Kulkarni, and A. Raz. Coronary tone modulation: formation and actions of prostaglandins, endoperoxides and thromboxanes. Science 195: 409–412, 1977.
 105. Needleman, P., G. R. Marshall, and J. R. Douglas, Jr. Prostaglandin release from vasculature by angiotensin II: Dissociation from lipolysis. European J. Pharmacol. 66: 316–319, 1973.
 106. Needleman, P., G. R. Marshall, and B. E. Sobel. Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin. Circulation Res. 37: 802–808, 1975.
 107. Needleman, P., M. Minkes, and A. Raz. Thromboxanes: selective biosynthesis and distinct biological properties. Science 193: 163–165, 1976.
 108. Needleman, P., S. Moncada, S. Bunting, J. R. Vane, M. Hamberg, and B. Samuelsson. Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature 261: 558–560, 1976.
 109. Needleman, P., A. Raz, J. A. Ferrendelli, and M. Minkes. Application of imidazole as a selective thromboxane synthetase inhibitor in human platelets. Proc. Natl. Acad. Sci. US 74: 716–720, 1977.
 110. Nugteren, D. H., and E. Hazelhof. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim. Biophys. Acta 326: 448–461, 1973.
 111. Olley, P. M. Nonsurgical palliation of congenital heart malformations. New Engl. J. Med. 292: 1292–1294, 1975.
 112. Olley, P. M., E. Bodach, J. Heaton, and F. Coceani. Further evidence implicating E‐type prostaglandins in the patency of the lamb ductus arteriosus. European J. Pharmacol. 34: 247–250, 1975.
 113. Olley, P. M., F. Coceani, and E. Bodach. E‐type prostaglandins: A new emergency therapy for certain cyanotic congenital heart malformations Circulation 53: 728–731, 1976.
 114. Pace‐Asciak, C. Prostaglandin synthetase activity in the rat stomach fundus. Activation by l‐norepinephrine and related compounds. Biochim. Biophys. Acta 280: 161–171, 1972.
 115. Pace‐Asciak, C. Letter: Isolation, structure and biosynthesis of 6‐ketoprostaglandin F1α in the rat stomach. J. Am. Chem. Soc. 98: 2348–2349, 1976.
 116. Pace‐Asciak, C., M. Nashat, and N. K. Menon. Transformation of prostaglandin G2 into 6(9)oxy‐11,15‐dihydroxy‐prosta‐7,13‐dienoic acid by rat stomach fundus. Biochim. Biophys. Acta 424: 323–325, 1976.
 117. Pace‐Asciak, C., and L. S. Wolfe. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry 10: 3657–3664, 1971.
 118. Park, M. K., C. Rishor, and D. C. Dyer. Vasoactive actions of prostaglandins and serotonin on isolated human umbilical arteries and veins. Can. J. Physiol. Pharmacol. 50: 393–399, 1972.
 119. Piper, P. J., and J. R. Vane. Release of additional factors in anaphylaxis and its antagonism by anti‐inflammatory drugs. Nature 223: 29–35, 1969.
 120. Piper, P., and J. R. Vane. The release of prostaglandins from lung and other tissues. Ann. NY Acad. Sci. 180: 363–385, 1971.
 121. Ramwell, P. W., J. E. Shaw, W. W. Douglas, and A. M. Poisner. Efflux of prostaglandin from adrenal glands stimulated with acetylcholine. Nature 210: 273–274, 1966.
 122. Raz, A., P. C. Isakson, M. S. Minkes, and P. Needleman. Characterization of a novel metabolic pathway of arachidonate in coronary arteries which generates a potent endogenous coronary vasodilator. J. Biol. Chem. 252: 1123–1126, 1977.
 123. Rioux, F., and D. Regoli. In vitro production of prostaglandins by isolated aorta strips of normotensive and hypertensive rats. Can. J. Physiol. Pharmacol. 53: 673–677, 1975.
 124. Samuelsson, B. On the incorporation of oxygen in the conversion of 8, 11, 14‐eicosatrienoic acid to prostaglandin E1. J. Am. Chem. Soc. 87: 3011–3013, 1965.
 125. Schweinitzer, E. M., and J. Brundell. Modification of canine vascular smooth muscle responses to dihydroergotamine by endogenous prostaglandin synthesis. European J. Pharmacol. 34: 197–206, 1975.
 126. Sharpe, G. L., K. S. Larsson, and B. Thalme. Studies on closure of the ductus arteriosus. XII. In utero effect of indomethacin and sodium salicylate in rats and rabbits. Prostaglandins 9: 585–596, 1975.
 127. Sharpe, G. L., B. Thalme, and K. J. Larsson. Studies on closure of the ductus arteriosus. XI. Ductal closure in utero by a prostaglandin synthetase inhibitor. Prostaglandins 8: 363–368, 1974.
 128. Starling, M. B., and R. B. Elliott. The effect of prostaglandins, prostaglandin inhibitors and oxygen on the closure of the ductus arteriosus, pulmonary arteries and umbilical vessels in vitro. Prostaglandins 8: 187–203, 1974.
 129. Strandberg, K., and T. Tuvemo. Reduction of the tone of the isolated human umbilical artery by indomethacin, eicosa‐5,8,11,14‐tetraynoic acid and polyphoretin phosphate. Acta Physiol. Scand. 94: 319–326, 1975.
 130. Strong, C. G., and D. F. Bohr. Effects of prostaglandins E1, E2, A1, and F1α on isolated vascular smooth muscle. Am. J. Physiol. 213: 725–733, 1967.
 131. Svensson, J., M. Hamberg, and B. Samuelsson. Prostaglandin endoperoxides. IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets. Acta Physiol. Scand. 94: 222–228, 1975.
 132. Terragno, D. A., K. Crowshaw, N. A. Terragno, and J. C. McGiff. Prostaglandin synthesis by bovine mesenteric arteries and veins. Circulation Res. 36–37: (Suppl. 1) 176–180, 1975.
 133. Terragno, N. A., D. A. Terragno, D. Pacholczyk, and J. C. McGiff. Prostaglandins and the regulation of uterine blood flow in pregnancy. Nature 249: 57–58, 1974.
 134. Toda, N., H. Usui, and K. Sakae. Different responses to prostaglandins E1 and E2 of isolated canine coronary arteries. Japan. J. Pharmacol. 25: 487–489, 1975.
 135. Tuvemo, T., K. Strandberg, M. Hamberg, and B. Samuelsson. Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery. Acta Physiol. Scand. 96: 145–149, 1976.
 136. Tuvemo, T., and L. Wide. Prostaglandin release from human umbilical artery in vitro. Prostaglandins 4: 689–694, 1973.
 137. Van Dorp, D. A., R. K. Beerthuis, D. A. Nugteren, and H. Vonkerman. Enzymatic conversion of all‐cis‐polyunsaturated fatty acids into prostaglandins. Nature 203: 839–841, 1964.
 138. Vane, J. R. The use of isolated organs for detecting active substances in the circulating blood. Brit. J. Pharmacol. 23: 360–373, 1964.
 139. Vane, J. R. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin‐like drugs. Nature New Biol. 231: 232–235, 1971.
 140. Vogt, W., T. Suzuki, and S. Babilli. Prostaglandins in SRS‐C and in darmstoff preparation from frog intestinal dialysates. Mem. Soc. Endocrinol. 14: 137–142, 1966.
 141. Von Euler, U. S. On the specific vasodilating and plain muscle stimulating substances from accessory genital glands in man and certain animals (prostaglandin and vesiglandin). J. Physiol. London 88: 213–234, 1936.
 142. Vonkeman, H., and D. A. Van Dorp. The action of prostaglandin synthetase on 2‐arachidonyl‐lecithin. Biochim. Biophys. Acta 164: 430–432, 1968.
 143. Weeks, J. R. Prostaglandins. In: Annual Review of Pharmacology, edited by H. W. Elliott, R. George, and R. Okun. Palo Alto, CA: Ann. Rev., 1972, vol. 12, p. 317–336.
 144. Weiner, R., and G. Kaley. Influence of prostaglandin E1 on the terminal vascular bed. Am. J. Physiol. 217: 563–566, 1969.
 145. Welch, K. M. A., L. Knowles, and P. Spira. Local effect of prostaglandins on cat pial arteries. European J. Pharmacol. 25: 155–158, 1974.
 146. Whodawer, P., H. Kindahl, and M. Hamberg. Biosynthesis of prostaglandin endoperoxides in the uterus. Biochim. Biophys. Acta 431: 603–614, 1976.
 147. Wolfe, L. S., H. M. Pappius, and J. Marion. The biosynthesis of prostaglandins by brain tissue in vitro. In: Advances in Prostaglandin and Thromboxane Research, edited by B. Samuelsson and R. Paoletti. New York: Raven, 1976, p. 345–356.
 148. Wong, P. Y. K., and J. C. McGiff. Enzymic regulation of prostaglandin levels in blood vessels: Relationship to cyclic GMP (Abstract). Federation Proc. 36: 673, 1977.
 149. Wong, P. Y. K., D. A. Terragno, N. A. Terragno, and J. C. McGiff. Prostaglandin‐related vascular effects of bradykinin: Relationship to cyclic GMP. Prostaglandins 13: 1113, 1977.
 150. Wong, P. Y. K., D. A. Terragno, N. A. Terragno, and J. C. McGiff. Dual effects of bradykinin on prostaglandin metabolism: Relationship to the dissimilar vascular actions of kinins. Prostaglandins 13: 1113–1126, 1977.

Contact Editor

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

* Required Field

Article Title: Intrinsic Prostaglandin Biosynthesis in Blood Vessels
 

How to Cite

Philip Needleman, Peter C. Isakson. Intrinsic Prostaglandin Biosynthesis in Blood Vessels. Compr Physiol 2011, Supplement 7: Handbook of Physiology, The Cardiovascular System, Vascular Smooth Muscle: 613-633. First published in print 1980. doi: 10.1002/cphy.cp020220