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.
- Adrenergic nerves
- CGRP-containing nerve
- Nicotinic acetylcholine receptor
ASJC Scopus subject areas