Mechanism of nicotine-induced relaxation in the porcine basilar artery.

The present experiment was designed to examine possible influence of adrenergic nerves on nicotine-induced neurogenic vasodilation in porcine basilar arteries denuded of endothelium. Nicotine and transmural nerve stimulation (TNS) induced relaxation of basilar arteries. Tetrodotoxin (TTX) abolished the relaxation elicited by TNS, but only partially blocked that induced by nicotine. Relaxation induced by both nicotine and TNS was abolished by N-nitro-L-arginine. The N-nitro-L-arginine inhibition of both TNS- and nicotine-induced relaxation was reversed by L-arginine but not by D-arginine. Hexamethonium abolished the relaxation induced by nicotine, but did not affect that elicited by TNS. Relaxation induced by nicotine was diminished by guanethidine, which did not affect the relaxation induced by TNS, suggesting that guanethidine blockade of nicotine-induced relaxation is not due to its local anesthetic effect. Results from histochemical studies indicated that catecholamine fluorescence and NADPH-diaphorase fibers were not appreciably affected by guanethidine. Following incubation with 6-hydroxydopamine for 1 hr, the catecholamine fluorescence fibers in the basilar arteries completely disappeared, although the NADPH-diaphorase fibers were not affected. In these adrenergically denervated arteries, nicotine-induced relaxation was abolished, while the TNS-elicited relaxation was not affected. Furthermore, norepinephrine-induced relaxation in basilar arteries was blocked by N-nitro-L-arginine, but was not affected by N-nitro-D-arginine or hexamethonium. These results suggest that in porcine cerebral arteries nicotine-induced nitric oxide-mediated relaxation is dependent on an intact adrenergic innervation. Nicotine appears to act on nicotinic receptors on the presynaptic adrenergic nerve terminals to release norepinephrine or a related substance, which then stimulates release of nitric oxide from the neighboring nitric oxidergic nerves. The TNS-elicited nitric oxide-mediated relaxation, however, is resulted from direct depolarization of nitric oxidergic nerves.