Interaction of endogenous nitric oxide and CGRP in sensory neuron-induced gastric vasodilation.
Stimulation of capsaicin-sensitive sensory nerves induces gastric mucosal hyperemia, which is mediated in part by both calcitonin gene-related peptide (CGRP) and nitric oxide (NO). In the present study, we used in vivo microscopy in anesthetized rats to determine 1) whether these agents were released locally at the submucosal level and, if so, 2) whether CGRP dilates arterioles via release of endothelium-derived NO. Intragastric capsaicin (160 microM) dilated submucosal arterioles from 25 +/- 3 to 67 +/- 8 microns. The intragastric capsaicin-induced vasodilation was markedly reversed not only by intravenous administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) but also by submucosal suffusion of either L-NAME or the CGRP receptor antagonist human CGRP-(8-37). The latter findings indicate that both NO and CGRP are released locally at the submucosal level. Submucosal application of CGRP induced dose-dependent dilation of gastric submucosal arterioles, which was significantly attenuated by L-NAME. However, at the same degree of vasodilation (42 microns), the dilation induced with submucosal CGRP was much less attenuated by NO synthesis inhibition (-28%) compared with that induced with intragastric capsaicin (-79%). This indicates that endothelium-derived NO released by CGRP was not the only source of submucosal NO in the latter response. There must be another as yet undetermined source of submucosal NO, e.g., possibly nitroxidergic nerves.
Chen
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Anesthesiology, Service, Veterans Affairs Medical Center West Los Angeles, California, USA.
Guth
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D000287:Administration, Topical; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D009569:Nitric Oxide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester