Abstract

We previously reported that nicotine-induced nitric oxide (NO)-mediated neurogenic vasodilation in the porcine basilar artery was dependent on intact sympathetic innervation. We further demonstrated in this artery that nicotine acted on nicotinic acetylcholine receptors (nAChRs) on presynaptic sympathetic nerve terminals to release norepinephrine (NE), which then acted on β₂-adrenoceptors located on the neighboring NOergic nerve terminals to release NO, resulting in vasodilation. The nature of the nAChRs has not been determined. The nAChR subtype mediating nicotine-induced dilation in isolated porcine basilar arterial rings denuded of endothelium was therefore examined pharmacologically and immunohistochemically. Results from using an in vitro tissue bath technique indicated that relaxation induced by nicotine (100 μM) was blocked by preferential α₇-nAChR antagonists (methyllycaconitine and α-bungarotoxin) and nonspecific nAChR antagonist (mecamylamine) in a concentration-dependent manner, but was not affected by dihydro-β-erythroidine (a preferential α₄-nAChR antagonist). These nAChR antagonists did not affect relaxation elicited by transmural nerve stimulation (8 Hz) or that by sodium nitroprusside and NE. Results from double-labeling immunohistochemical studies in whole-mount porcine basilar and middle cerebral arteries and in cultured porcine superior cervical ganglia (SCG) indicated that α₇-nAChR- and tyrosine hydroxylase immunoreactivities were colocalized in same nerve fibers. These results suggest the presence of functional α₇-nAChRs on postganglionic sympathetic adrenergic nerve terminals of SCG origin, which mediate nicotine-induced neurogenic NOergic vasodilation. These findings are consistent with our hypothesis that nicotine acts on nAChRs on presynaptic sympathetic nerve terminals to release NE, which then acts on presynaptic β₂-adrenoceptors located on the neighboring NOergic nerve terminals, resulting in release of NO and dilation of porcine basilar arteries.