Regulation of distal esophageal mucosal blood flow: The roles of nitric oxide and substance P

A. D. Sandler, C. Schmidt, K. Richardson, Joseph A Murray, J. W. Maher, P. C. Donahue, B. L. Bass, S. J. Mulvihill

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background. An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. Methods. Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. Results. Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). N(G)-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.01) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). Conclusions. Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.

Original languageEnglish (US)
Pages (from-to)285-294
Number of pages10
JournalSurgery
Volume114
Issue number2
StatePublished - 1993
Externally publishedYes

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Substance P
Hydrochloric Acid
Nitric Oxide
Capsaicin
Esophagus
Manometry
Bradykinin
Denervation
Vasodilation
Synaptic Transmission
Cholinergic Agents
Blood Vessels
Lasers
Dogs
Neurons
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

Cite this

Sandler, A. D., Schmidt, C., Richardson, K., Murray, J. A., Maher, J. W., Donahue, P. C., ... Mulvihill, S. J. (1993). Regulation of distal esophageal mucosal blood flow: The roles of nitric oxide and substance P. Surgery, 114(2), 285-294.

Regulation of distal esophageal mucosal blood flow : The roles of nitric oxide and substance P. / Sandler, A. D.; Schmidt, C.; Richardson, K.; Murray, Joseph A; Maher, J. W.; Donahue, P. C.; Bass, B. L.; Mulvihill, S. J.

In: Surgery, Vol. 114, No. 2, 1993, p. 285-294.

Research output: Contribution to journalArticle

Sandler, AD, Schmidt, C, Richardson, K, Murray, JA, Maher, JW, Donahue, PC, Bass, BL & Mulvihill, SJ 1993, 'Regulation of distal esophageal mucosal blood flow: The roles of nitric oxide and substance P', Surgery, vol. 114, no. 2, pp. 285-294.
Sandler AD, Schmidt C, Richardson K, Murray JA, Maher JW, Donahue PC et al. Regulation of distal esophageal mucosal blood flow: The roles of nitric oxide and substance P. Surgery. 1993;114(2):285-294.
Sandler, A. D. ; Schmidt, C. ; Richardson, K. ; Murray, Joseph A ; Maher, J. W. ; Donahue, P. C. ; Bass, B. L. ; Mulvihill, S. J. / Regulation of distal esophageal mucosal blood flow : The roles of nitric oxide and substance P. In: Surgery. 1993 ; Vol. 114, No. 2. pp. 285-294.
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title = "Regulation of distal esophageal mucosal blood flow: The roles of nitric oxide and substance P",
abstract = "Background. An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. Methods. Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5{\%}) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. Results. Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). N(G)-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.01) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). Conclusions. Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.",
author = "Sandler, {A. D.} and C. Schmidt and K. Richardson and Murray, {Joseph A} and Maher, {J. W.} and Donahue, {P. C.} and Bass, {B. L.} and Mulvihill, {S. J.}",
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T1 - Regulation of distal esophageal mucosal blood flow

T2 - The roles of nitric oxide and substance P

AU - Sandler, A. D.

AU - Schmidt, C.

AU - Richardson, K.

AU - Murray, Joseph A

AU - Maher, J. W.

AU - Donahue, P. C.

AU - Bass, B. L.

AU - Mulvihill, S. J.

PY - 1993

Y1 - 1993

N2 - Background. An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. Methods. Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. Results. Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). N(G)-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.01) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). Conclusions. Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.

AB - Background. An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. Methods. Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. Results. Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). N(G)-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.01) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). Conclusions. Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.

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