Adrenergic nerves mediate acetylcholine-induced endothelium-independent vasodilation in the rat mesenteric resistance artery

Mechanisms underlying acetylcholine-induced endothelium-independent vasodil ation 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 muM), perfusion of acetylcholin e (1-100 muM) for I min produced a concentration-dependent vasodilation. De nervation of denuded preparations by cold storage (4 degreesC for 72 h) abo lished the acetylcholine-induced vasodilation; 10 and 100 nM atropine aboli shed 1 and 10 muM acetylcholine-induced vasodilation, but it inhibited only 20% of vasodilation by 100 muM acetylcholine. The acetylcholine-induced at ropine-resistant vasodilation was inhibited by 10 and 100 muM hexamethonium , 5 muM guanethidine, 50 muM bretylium, in vitro 6-hydroxydopamine (2 mM fo r 20 min, twice), I muM capsaicin and 0.5 muM calcitonin gene-related pepti de (CGRP)-(8-37) (CGRP receptor antagonist). These findings suggest that th e acetylcholine-induced endothelium-independent nicotinic vasodilation requ ires the presence of intact adrenergic nerves, and is mediated by endogenou s CGRP released from CGRP-containing nerves. (C) 2001 Elsevier Science B.V. All rights reserved.