Analysis of the vasodilator nerve function by nicotine in isolated dog skin artery.
Mechanisms underlying the relaxation induced by nicotine were analyzed in cutaneous arterial strips isolated from dogs and with the endothelium removed. In the strips treated with prazosin and precontracted with prostaglandin F2 alpha, nicotine produced relaxations which were not influenced by atropine but abolished by hexamethonium. Relaxations induced by nicotine were partially inhibited by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the remaining relaxations were abolished by desensitization to calcitonin gene-related peptide (CGRP) or treatment with CGRP-(8-37), a CGRP receptor antagonist, or with capsaicin. Desensitization to vasoactive intestinal polypeptide (VIP) or a VIP receptor antagonist did not influence the nicotine-induced relaxation. In the strips densensitized to CGRP, the nicotine-induced relaxation was abolished by L-NA; the inhibitory effect was reversed by L-arginine. Perivascular nerves containing NADPH diaphorase and CGRP immunoreactivity were histochemically identified in the cutaneous artery. CGRP immunoreactivity was abolished by treatment with capsaicin. It is concluded that nicotine produces relaxation in dog cutaneous arterial strips, possibly mediated by NO and CGRP liberated from vasodilator nerves.
Uchiyama
M
M
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Okamura
T
T
Uehara
M
M
Toda
N
N
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000294:innervation*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D018722:Nicotinic Agonists; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine; D015740:Calcitonin Gene-Related Peptide