The role of calcitonin gene-related peptide and nitric oxide in gastric mucosal hyperemia and protection.
It has been suggested that capsaicin-induced hyperemia and mucosal protection occurs via calcitonin-gene-related peptide (CGRP) release from gastric afferent sensory neurons and nitric oxide (NO)-mediated vasodilation. The purpose of this study was to determine whether capsaicin and/or bile acid induced hyperemia is mediated by CGRP and/or NO. Male Sprague-Dawley rats (280-350 g) were anesthetized, and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into six groups. Normal saline (groups 1 and 4), the NO inhibitor N-nitro-L-arginine methyl ester (L-NAME; 3.75 mg/ml, groups 2 and 5), or the CGRP antagonist hCGRP8-37 (0.047 mg/ml, groups 3 and 6) was continuously infused intraarterially (ia) close to the stomach at a rate of 0.034 ml/min for 1 hr via a catheter inserted retrogradely into the splenic artery. Fifteen minutes after the onset of this infusion, the gastric mucosa was topically exposed to neutral saline solution for 15 min, followed by 160 microM capsaicin for 15 min. The mucosa was then injured by a 15-min exposure to either 5 mM acidified taurocholate (ATC, pH 1.2) in groups 1-3 or 10 mM ATC in groups 4-6. Gastric mucosal blood flow (ml/min/100 g) was continuously measured (laser doppler), and injury was assessed by measuring net transmucosal H+ flux, luminal accumulation of DNA, and histologic grading (0 = no injury to 3 = severe) by an independent observer. Intraarterial infusion of L-NAME significantly blocked the hyperemic response of topical capsaicin while having minimal effect on bile acid-induced hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Merchant
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Reichle Surgical Research Laboratory, Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania 19140.
Goodman
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J
Dempsey
D T
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Milner
R E
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Ritchie
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WP
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001647:Bile Acids and Salts; D001783:Blood Flow Velocity; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin; D004247:DNA / Q000378:metabolism; D004058:Diffusion; D005753:Gastric Mucosa / Q000098:blood supply* / Q000473:pathology; D006940:Hyperemia / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
D001647:Bile Acids and Salts; D010446:Peptide Fragments; D011522:Protons; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D004247:DNA; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester