MECHANISMS UNDERLYING CONSTRICTOR AND DILATOR RESPONSES TO PERIVASCULAR NERVE-STIMULATION IN CANINE LINGUAL ARTERIES

In isolated canine lingual arteries denuded of the endothelium, transm ural electrical stimulation (2-20 Hz) produced a frequency-related con traction which was not significantly influenced by prazosin but which was reversed to a relaxation by alpha,beta-methylene ATP. The response s were abolished by tetrodotoxin. The stimulation-induced relaxation w as abolished by treatment with N-G-nitro-L-arginine (L-NA, 10(-6) M) a nd restored by the addition of L-arginine. Neurogenic relaxation resis tant to L-NA was not observed after electrical stimulation, even thoug h the pulse width and stimulus intensity were raised. Under treatment with prazosin, alpha,beta-methylene ATP and indomethacin, the arterial strips responded to nicotine (10(-4) M) with a marked relaxation that was abolished by hexamethonium. The relaxation was significantly inhi bited but not abolished by L-NA (10(-5) M), and raising the concentrat ion of the inhibitor to 10(-4) M, did not produce additional inhibitio n. In the strips treated with L-NA, the nicotine-induced relaxation wa s abolished or markedly reduced under desensitization with vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP) and by treatment with high concentrations of beraprost, a stable analog o f prostaglandin I-2, but was unaffected by CGRP or VIP receptor antago nists. Relaxant responses to a low concentration of nicotine (5 x 10(- 6) M) were abolished by L-NA and restored by L-arginine. Histochemical study demonstrated many nerve fibers and bundles containing NADPH dia phorase in the adventitia of the arteries. It is concluded that the ne urogenic arterial contraction is induced mainly by ATP via stimulation of P2X purinoceptors, and that the relaxation induced by electrical s timulation or a low concentration of nicotine is mediated by nitric ox ide (NO) released from perivascular nerves. In high concentrations, ni cotine elicits marked relaxations possibly due to the liberation of NO from the nerve and also vasodilator substances that increase the cont ent of cyclic AMP in the tissue; CGRP and VIP are unlikely to be invol ved. (C) 1998 Elsevier Science B.V. All rights reserved.