Nitric oxide regulates basal but not capsaicin-, CGRP-, or bile salt-stimulated rabbit esophageal mucosal blood flow.
OBJECTIVE
Esophageal mucosal blood flow is a dynamic phenomenon that is altered by luminal content that probably represents an important intrinsic method of defense. This study investigated the role played by endogenous nitric oxide in the regulation of esophageal mucosal blood flow at rest and in response to luminal capsaicin, a specific stimulant for visceral afferent nerves, as well as calcitonin gene-related peptide, and the bile salt deoxycholate.


METHODS
The L-arginine analog L-NAME was used to block nitric oxide synthesis. Radiolabeled microspheres were used to measure blood flow in a well-characterized rabbit model. Phenylephrine was used to mimic the hemodynamic effects of L-NAME to show the specificity of positive findings.


RESULTS
Administration of L-NAME led to a significant reduction in mucosal blood flow at rest, an effect that was not shared by phenylephrine. The blood flow responses to luminal capsaicin, intra-arterial calcitonin gene-related peptide (CGRP), and luminal deoxycholate, however, were not diminished in the presence of L-NAME.


CONCLUSIONS
Although nitric oxide may play a role in the maintenance of normal resting esophageal mucosal blood flow, the reactive responses to luminal capsaicin, luminal deoxycholate, and intra-arterial CGRP are not nitric oxide dependent.
McKie
L D
LD
Department of Surgery, VA Medical Center, Washington, District of Columbia 20422, USA.
Bass
B L
BL
Dunkin
B J
BJ
Harmon
J W
JW
D000287:Administration, Topical; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000494:pharmacology*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004947:Esophagus / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation; D006940:Hyperemia / Q000139:chemically induced / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008863:Microspheres; D009092:Mucous Membrane; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D003840:Deoxycholic Acid; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester