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

Abstract

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 μM), perfusion of acetylcholine (1–100 μM) for 1 min produced a concentration-dependent vasodilation. Denervation of denuded preparations by cold storage (4°C for 72 h) abolished the acetylcholine-induced vasodilation; 10 and 100 nM atropine abolished 1 and 10 μM acetylcholine-induced vasodilation, but it inhibited only 20% of vasodilation by 100 μM acetylcholine. The acetylcholine-induced atropine-resistant vasodilation was inhibited by 10 and 100 μM hexamethonium, 5 μM guanethidine, 50 μM bretylium, in vitro 6-hydroxydopamine (2 mM for 20 min, twice), 1 μM capsaicin and 0.5 μM 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.