Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent vasodilation induced by nicotine in mesenteric resistance arteries ofthe rat

1 The mechanisms underlying vasodilator effect of nicotine on mesenteric re sistance blood vessels and the role of calcitonin gene-related peptide (CGR P)-containing (CGRPergic) vasodilator nerves were studied in the rat. 2 Mesenteric vascular beds isolated from Wistar rats were perfused with Kre bs solution, and perfusion pressure was measured with a pressure transducer . 3 In preparations with intact endothelium and contracted by perfusion with Krebs solution containing methoxamine, perfusion of nicotine (1-100 mu M) f or 1 min caused a concentration-dependent vasodilator response without vaso constriction. 4 The nicotine-induced vasodilation was markedly inhibited by hexamethonium (nicotinic cholinoceptor antagonist, 10 mu M) and blocked by guanethidine (adrenergic neuron blocker, 5 mu M). 5 Either denervation by cold storage (4 degrees C for 72h) or adrenergic de nervation by 6-hydroxydopamine (toxin for adrenergic neurons, 2 mM for 20 m in incubation, twice) blocked the nicotine-induced vasodilation. 6 Neither endothelium removal with perfusion of sodium deoxycholate (1.80 m g ml(-1), for 30 s) nor treatment with N-omega-nitro-L-arginine (nitric oxi de synthase inhibitor, 100 mu M), atropine (muscarinic cholinoceptor antago nist, 10 nM) or propranolol (beta-adrenoceptor antagonist, 100 nM) affected the nicotine-induced vasodilation. 7 In preparations without endothelium, treatment with capsaicin (depleting CGRP-containing sensory nerves, 1 mu M) Or human CGRP[8-37] (CGRP receptor antagonist, 0.5 mu M) markedly inhibited the nicotine-induced vasodilation. 8 These results suggest that, in the mesenteric resistance artery of the ra t, nicotine induces vasodilation, which is independent of the function of t he endothelium and is involved in activation of CGRPergic nerves. It is als o suggested that nicotine stimulates presynaptic nicotinic cholinoceptors o n adrenergic nerves to release adrenergic neurotransmitters, which then act on CGRPergic nerves to release endogenous CGRP from the nerve.