Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilation.
The response of gastric submucosal arterioles to topical (submucosal) application of calcitonin-gene-related peptide (CGRP) or capsaicin with and without the human CGRP antagonist, hCGRP-(8-37), was studied using in vivo microscopy. CGRP (10(-11) to 10(-8) M) induced dose-dependent dilation. Topical treatment with hCGRP(8-37) (10(-6) M, for 10 min) caused a significant decrease in basal arteriolar diameter from 33 +/- 2 to 27 +/- 2 microns. hCGRP(8-37) did not alter acetylcholine- or adenosine-induced vasodilation but did significantly reduce CGRP 10(-8) M vasodilation from 97.3 +/- 10.1 to 15.9 +/- 4.4% of the maximal response. Topical capsaicin (10(-9) M to 5 x 10(-7) M) induced dose-dependent arteriolar dilation. This vasodilation was markedly attenuated by hCGRP(8-37). Selective ablation of capsaicin-sensitive sensory neurons nearly completely inhibited capsaicin-induced vasodilation, suggesting that this vasodilation is primarily neurogenic in origin. We conclude that 1) topical application of capsaicin stimulates capsaicin-sensitive sensory neurons and induces dose-dependent arteriolar dilation; 2) this vasodilation is mediated in part by CGRP; and 3) CGRP may be involved in modulating the basal tone of gastric resistance vessels.
Chen
R Y
RY
Anesthesiology Service, Veterans Affairs Medical Center, West Los Angeles, California.
Li
D S
DS
Guth
P H
PH
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000294:innervation; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D003714:Denervation; D005753:Gastric Mucosa / Q000098:blood supply*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin