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Reflexes Evoked from Tracheobronchial Tree and Lungs

H. M. Coleridge, J. C. G. Coleridge

10.1002/cphy.cp030212

Source: Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing

Originally published: 1986

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Afferent Endings in Tracheobronchial Tree and Lungs
1.1 Slowly Adapting Pulmonary Stretch Receptors
1.2 Rapidly Adapting Stretch (Irritant) Receptors
1.3 Pulmonary and Bronchial C‐Fibers
2 Reflexes
2.1 Reflexes Evoked by Volume Changes
2.2 Reflexes Evoked by Chemicals
Figure 1. Figure 1.

Schematic drawing of slowly adapting pulmonary stretch receptor in rat bronchus wall based on light and electron microscopy. Receptor is supplied by myelinated fiber (mf). Bundle of nonmyelinated fibers (n) and their terminals (sy) accompany the stretch receptor and are believed to be efferent. cf, Collagen fiber; ef, elastic network; sm, smooth muscle; e, respiratory epithelium.

From von During et al. 262
Figure 2. Figure 2.

Camera lucida drawing of terminal arborization of a myelinated fiber in bronchial epithelium of dog. This is believed to represent typical appearance of rapidly adapting (irritant) receptor 242,252.

From Elftman 81
Figure 3. Figure 3.

Response of rapidly adapting (irritant) receptor in dog to inflation of lung at successively increasing rates of airflow.

From Pack 176. Reproduced, with permission, from the Annual Review of Physiology, Volume 43. © 1981 by Annual Reviews, Inc
Figure 4. Figure 4.

Response of irritant receptor to right atrial injection of histamine acid phosphate 100 μg · kg−1 (at signal in uppermost record of each section) in vagotomized, paralyzed, and artificially ventilated rabbit. A: before administration of 50 μg of isoprenaline to prevent bronchoconstriction. B: after administration. After isoprenaline, response of irritant receptor (large action potentials) is reduced to a few impulses. In A, interval of 5.5 s between upper two traces and 20.5 s between lower two. In B, corresponding intervals were 4 s and 20 s. Origin of small action potentials visible in both A and B is not recorded. Vt, tidal volume; BP, blood pressure.

From Mills et al. 159
Figure 5. Figure 5.

Response of rapidly adapting (irritant) receptor (large spikes) and C‐fiber ending (small spikes) to prostaglandins in open‐chest artificially ventilated dog. Both endings were located in lower lobe of left lung. A: before right atrial injection of prostaglandin F2α (4 μg·kg−1). B: 16 s after injection. Interval of 6 min between B and C. C and D: before and 42 s after right atrial injection of prostaglandin E2 (20 μg·kg−1), respectively. From top to bottom in each record: 1‐s time trace; ECG, electrocardiogram; AP, action potentials recorded from filament of left vagus nerve; Pt, tracheal pressure.

From Coleridge et al. 45. Reprinted by permission from Nature London, Vol. 264, p. 451–453, © 1976 MacMillan Journals Limited
Figure 6. Figure 6.

Response of rapidly adapting receptor (large spikes) and bronchial C‐fiber (small spikes) to bradykinin in open‐chest artificially ventilated dog. Both endings were located in left lung. Bradykinin (1 μg·kg−1) was injected into left atrium at signal in A. Records A and B are continuous. AP, action potentials recorded from left vagus nerve; ABP, arterial blood pressure; Pt, tracheal pressure.

From Kaufman et al. 133
Figure 7. Figure 7.

Top: technique for stimulating bronchial C‐fibers in dog by injecting small amounts of bradykinin (BK) into right bronchial artery and for examining reflex effects on airway smooth muscle by recording tension in upper tracheal segment. Each lateral cut edge of tracheal segment (TS) is attached by threads to light but rigid plastic bar. One bar is attached to fixed metal rod and the other to an isometric force transducer (FT). Segment is innervated only by superior laryngeal nerves (SLN); recurrent laryngeal nerves (RLN) are cut. Right bronchial artery (Br A) lies dorsal (dotted line) to right lung root. Smaller diagram on left depicts right bronchial artery stemming from intercostal artery (Int A), which arises from descending thoracic aorta (Ao). Bradykinin injected retrogradely into intercostal artery passes into bronchial artery. Each cervical vagus nerve (VN) is placed on a cooling platform (CP). Bottom: effect of injecting 1.5 μg of BK on activity in right vagal filament containing 3 bronchial C‐fibers with endings in right lung. AP, action potentials; ABP, arterial blood pressure; Pt, tracheal pressure. Time, 1 s. [From Kaufman et al. 133.]

From Roberts et al. 202
Figure 8. Figure 8.

Comparison in dog of effects on breathing frequency of reinflation of lung in steps after passive deflation (control) and after collapse by suction (collapsed lung) during cardiopulmonary bypass. Breathing frequency is measured from phrenic neurogram. Airway pressure is increased in steps of 1.25 mmHg from 0 to 7.5 mmHg after passive lung deflation and from 0 to 10 mmHg after collapse by suction. In former case changes in breathing frequency are linearly related to airway pressure, and in latter case transmural pressure of ∼6 mmHg is required before changes in frequency are obtained; at this point collapsed peripheral segments of lung are reinflated.

From Nilsestuen et al. 174
Figure 9. Figure 9.

Effect of SO2‐induced block of slowly adapting stretch receptors on breathing pattern in rabbit compared with effect of vagotomy. BP, blood pressure; Vt, tidal volume (with some integrator drift); Ptp, transpulmonary pressure; V, airflow.

From Davies et al. 66
Figure 10. Figure 10.

Effect of SO2‐induced block of slowly adapting stretch receptors on deflation reflex in rabbits, i.e., on reflex involving selective stimulation of rapidly adapting (irritant) receptors 253. A 40‐ml pneumothorax is induced during horizontal bars. Top: control; note tachypnea and augmented breath. Bottom: block of slowly adapting stretch receptors. Note absence of tachypnea but prolongation of inspiratory time at onset of pneumothorax and augmented breath at removal. BP, blood pressure; Vt, tidal volume.

From Davies et al. 66
Figure 11. Figure 11.

Effect of intravenous injection of 150 μg of phenyl diguanide (top) and 150 μg of histamine acid phosphate (bottom) on blood pressure (BP), tidal volume (Vt), and phrenic action potentials in cat. Chemical was injected at first signal and was washed in with saline at second signal. Note prompt onset of apnea and subsequent rapid shallow breathing after injection of phenyl diguanide. Note also delayed onset of rapid shallow breathing and augmented breath after injection of histamine. Cardiac slowing occurred after both injections but was delayed after injection of histamine.

From Winning and Widdicombe 257
Figure 12. Figure 12.

Effect on breathing pattern of 150 μg of phenyl diguanide and histamine acid phosphate given intravenously to cat first made hypopneic by being hyperventilated to apnea and then rebreathing O2 to cause hypercapnic hyperpnea. Vagus nerves were intact. A: relationship between tidal volume (Vt) and inspiratory time (Ti). ○, Control relationship produced by rebreathing O2 after apnea; •, rebreathing O2 after phenyl diguanide had been injected in preceding apneic period; +, rebreathing O2 after similar injection of histamine. B: relationship between Ti and expiratory time (Te), x, Control eupneic breaths; ○, control hyperpneic breaths (rebreathing O2); ▴, breaths produced by histamine during eupnea; +, breaths produced by histamine during hyperpnea; •, breaths produced by phenyl diguanide during eupnea; ▪, breaths produced by phenyl diguanide during hyperpnea.

From Winning and Widdicombe 257
Figure 13. Figure 13.

Effect of injecting bradykinin into right bronchial artery on smooth muscle tone in upper tracheal segment of dog. Recurrent laryngeal nerves are cut so that segment is innervated only by superior laryngeal nerves. (See Fig. 8 for diagram of preparation.) A‐E: bradykinin (1.5 μg) is injected into bronchial artery at signal. A: both vagi at 36°C. B: vagi cooled to 7°C. Note increase in base‐line tension. C: vagi cooled to 0°‐1°C. Note decrease in base‐line tension. D: vagi rewarmed. Between D and E: both cervical vagus nerves are cut. E: response to bradykinin is abolished by vagotomy. F: tracheal contraction can still be evoked reflexly when carotid bodies are stimulated by ventilating lungs with 5% O2 in N2 (At all other times in A‐F, lungs are ventilated with 50% O2 in air.) In A and D, initial base‐line tracheal tension is set at 50 g; it is not adjusted in B, C, or E. Note changes in tracheal pressure; lungs briefly hyperinflated between A and B and between C and D. Reduced response after vagal cooling to 7°C (A, B) is not caused by blockade of myelinated vagal afferents but by temperature‐dependent decrease in firing frequency in afferent C‐fibers 50. Vagal temp., temperature of cervical vagus nerves; ABP, arterial blood pressure; HR, heart rate; Tr tension, tracheal tension in grams above resting base‐line tension; Pt, tracheal pressure.

From Roberts et al. 202


Figure 1.

Schematic drawing of slowly adapting pulmonary stretch receptor in rat bronchus wall based on light and electron microscopy. Receptor is supplied by myelinated fiber (mf). Bundle of nonmyelinated fibers (n) and their terminals (sy) accompany the stretch receptor and are believed to be efferent. cf, Collagen fiber; ef, elastic network; sm, smooth muscle; e, respiratory epithelium.

From von During et al. 262


Figure 2.

Camera lucida drawing of terminal arborization of a myelinated fiber in bronchial epithelium of dog. This is believed to represent typical appearance of rapidly adapting (irritant) receptor 242,252.

From Elftman 81


Figure 3.

Response of rapidly adapting (irritant) receptor in dog to inflation of lung at successively increasing rates of airflow.

From Pack 176. Reproduced, with permission, from the Annual Review of Physiology, Volume 43. © 1981 by Annual Reviews, Inc


Figure 4.

Response of irritant receptor to right atrial injection of histamine acid phosphate 100 μg · kg−1 (at signal in uppermost record of each section) in vagotomized, paralyzed, and artificially ventilated rabbit. A: before administration of 50 μg of isoprenaline to prevent bronchoconstriction. B: after administration. After isoprenaline, response of irritant receptor (large action potentials) is reduced to a few impulses. In A, interval of 5.5 s between upper two traces and 20.5 s between lower two. In B, corresponding intervals were 4 s and 20 s. Origin of small action potentials visible in both A and B is not recorded. Vt, tidal volume; BP, blood pressure.

From Mills et al. 159


Figure 5.

Response of rapidly adapting (irritant) receptor (large spikes) and C‐fiber ending (small spikes) to prostaglandins in open‐chest artificially ventilated dog. Both endings were located in lower lobe of left lung. A: before right atrial injection of prostaglandin F2α (4 μg·kg−1). B: 16 s after injection. Interval of 6 min between B and C. C and D: before and 42 s after right atrial injection of prostaglandin E2 (20 μg·kg−1), respectively. From top to bottom in each record: 1‐s time trace; ECG, electrocardiogram; AP, action potentials recorded from filament of left vagus nerve; Pt, tracheal pressure.

From Coleridge et al. 45. Reprinted by permission from Nature London, Vol. 264, p. 451–453, © 1976 MacMillan Journals Limited


Figure 6.

Response of rapidly adapting receptor (large spikes) and bronchial C‐fiber (small spikes) to bradykinin in open‐chest artificially ventilated dog. Both endings were located in left lung. Bradykinin (1 μg·kg−1) was injected into left atrium at signal in A. Records A and B are continuous. AP, action potentials recorded from left vagus nerve; ABP, arterial blood pressure; Pt, tracheal pressure.

From Kaufman et al. 133


Figure 7.

Top: technique for stimulating bronchial C‐fibers in dog by injecting small amounts of bradykinin (BK) into right bronchial artery and for examining reflex effects on airway smooth muscle by recording tension in upper tracheal segment. Each lateral cut edge of tracheal segment (TS) is attached by threads to light but rigid plastic bar. One bar is attached to fixed metal rod and the other to an isometric force transducer (FT). Segment is innervated only by superior laryngeal nerves (SLN); recurrent laryngeal nerves (RLN) are cut. Right bronchial artery (Br A) lies dorsal (dotted line) to right lung root. Smaller diagram on left depicts right bronchial artery stemming from intercostal artery (Int A), which arises from descending thoracic aorta (Ao). Bradykinin injected retrogradely into intercostal artery passes into bronchial artery. Each cervical vagus nerve (VN) is placed on a cooling platform (CP). Bottom: effect of injecting 1.5 μg of BK on activity in right vagal filament containing 3 bronchial C‐fibers with endings in right lung. AP, action potentials; ABP, arterial blood pressure; Pt, tracheal pressure. Time, 1 s. [From Kaufman et al. 133.]

From Roberts et al. 202


Figure 8.

Comparison in dog of effects on breathing frequency of reinflation of lung in steps after passive deflation (control) and after collapse by suction (collapsed lung) during cardiopulmonary bypass. Breathing frequency is measured from phrenic neurogram. Airway pressure is increased in steps of 1.25 mmHg from 0 to 7.5 mmHg after passive lung deflation and from 0 to 10 mmHg after collapse by suction. In former case changes in breathing frequency are linearly related to airway pressure, and in latter case transmural pressure of ∼6 mmHg is required before changes in frequency are obtained; at this point collapsed peripheral segments of lung are reinflated.

From Nilsestuen et al. 174


Figure 9.

Effect of SO2‐induced block of slowly adapting stretch receptors on breathing pattern in rabbit compared with effect of vagotomy. BP, blood pressure; Vt, tidal volume (with some integrator drift); Ptp, transpulmonary pressure; V, airflow.

From Davies et al. 66


Figure 10.

Effect of SO2‐induced block of slowly adapting stretch receptors on deflation reflex in rabbits, i.e., on reflex involving selective stimulation of rapidly adapting (irritant) receptors 253. A 40‐ml pneumothorax is induced during horizontal bars. Top: control; note tachypnea and augmented breath. Bottom: block of slowly adapting stretch receptors. Note absence of tachypnea but prolongation of inspiratory time at onset of pneumothorax and augmented breath at removal. BP, blood pressure; Vt, tidal volume.

From Davies et al. 66


Figure 11.

Effect of intravenous injection of 150 μg of phenyl diguanide (top) and 150 μg of histamine acid phosphate (bottom) on blood pressure (BP), tidal volume (Vt), and phrenic action potentials in cat. Chemical was injected at first signal and was washed in with saline at second signal. Note prompt onset of apnea and subsequent rapid shallow breathing after injection of phenyl diguanide. Note also delayed onset of rapid shallow breathing and augmented breath after injection of histamine. Cardiac slowing occurred after both injections but was delayed after injection of histamine.

From Winning and Widdicombe 257


Figure 12.

Effect on breathing pattern of 150 μg of phenyl diguanide and histamine acid phosphate given intravenously to cat first made hypopneic by being hyperventilated to apnea and then rebreathing O2 to cause hypercapnic hyperpnea. Vagus nerves were intact. A: relationship between tidal volume (Vt) and inspiratory time (Ti). ○, Control relationship produced by rebreathing O2 after apnea; •, rebreathing O2 after phenyl diguanide had been injected in preceding apneic period; +, rebreathing O2 after similar injection of histamine. B: relationship between Ti and expiratory time (Te), x, Control eupneic breaths; ○, control hyperpneic breaths (rebreathing O2); ▴, breaths produced by histamine during eupnea; +, breaths produced by histamine during hyperpnea; •, breaths produced by phenyl diguanide during eupnea; ▪, breaths produced by phenyl diguanide during hyperpnea.

From Winning and Widdicombe 257


Figure 13.

Effect of injecting bradykinin into right bronchial artery on smooth muscle tone in upper tracheal segment of dog. Recurrent laryngeal nerves are cut so that segment is innervated only by superior laryngeal nerves. (See Fig. 8 for diagram of preparation.) A‐E: bradykinin (1.5 μg) is injected into bronchial artery at signal. A: both vagi at 36°C. B: vagi cooled to 7°C. Note increase in base‐line tension. C: vagi cooled to 0°‐1°C. Note decrease in base‐line tension. D: vagi rewarmed. Between D and E: both cervical vagus nerves are cut. E: response to bradykinin is abolished by vagotomy. F: tracheal contraction can still be evoked reflexly when carotid bodies are stimulated by ventilating lungs with 5% O2 in N2 (At all other times in A‐F, lungs are ventilated with 50% O2 in air.) In A and D, initial base‐line tracheal tension is set at 50 g; it is not adjusted in B, C, or E. Note changes in tracheal pressure; lungs briefly hyperinflated between A and B and between C and D. Reduced response after vagal cooling to 7°C (A, B) is not caused by blockade of myelinated vagal afferents but by temperature‐dependent decrease in firing frequency in afferent C‐fibers 50. Vagal temp., temperature of cervical vagus nerves; ABP, arterial blood pressure; HR, heart rate; Tr tension, tracheal tension in grams above resting base‐line tension; Pt, tracheal pressure.

From Roberts et al. 202
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Article Title: Reflexes Evoked from Tracheobronchial Tree and Lungs
 

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H. M. Coleridge, J. C. G. Coleridge. Reflexes Evoked from Tracheobronchial Tree and Lungs. Compr Physiol 2011, Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing: 395-429. First published in print 1986. doi: 10.1002/cphy.cp030212