Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery.
Mechanisms underlying acetylcholine-induced endothelium-independent vasodilation were studied in the rat mesenteric vascular bed isolated from Wistar rats. In preparations without endothelium, and contracted by perfusion with Krebs solution containing methoxamine (2-7 microM), perfusion of acetylcholine (1-100 microM) for 1 min produced a concentration-dependent vasodilation. Denervation of denuded preparations by cold storage (4 degrees C for 72 h) abolished the acetylcholine-induced vasodilation; 10 and 100 nM atropine abolished 1 and 10 microM acetylcholine-induced vasodilation, but it inhibited only 20% of vasodilation by 100 microM acetylcholine. The acetylcholine-induced atropine-resistant vasodilation was inhibited by 10 and 100 microM hexamethonium, 5 microM guanethidine, 50 microM bretylium, in vitro 6-hydroxydopamine (2 mM for 20 min, twice), 1 microM capsaicin and 0.5 microM calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist). These findings suggest that the acetylcholine-induced endothelium-independent nicotinic vasodilation requires the presence of intact adrenergic nerves, and is mediated by endogenous CGRP released from CGRP-containing nerves.
Shiraki
H
H
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, Japan.
Kawasaki
H
H
Tezuka
S
S
Nakatsuma
A
A
Nawa
H
H
Araki
H
H
Gomita
Y
Y
Kurosaki
Y
Y
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010276:Parasympatholytics; D010446:Peptide Fragments; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine