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CARDIOVASCULAR

Pb²⁺ Inhibition of Sympathetic ₇-Nicotinic Acetylcholine Receptor-Mediated Nitrergic Neurogenic Dilation in Porcine Basilar Arteries

Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois (M.-L.S., T.J.-F.L.); and College of Life Sciences and Neuro-Medical Scientific Center, Tzu Chi University, Hualien, Taiwan (T.J.-F.L.)

Chronic exposure to inorganic lead (Pb²⁺) has been shown to facilitate peripheral vasoconstriction causing hypertension. Effect of lead on cerebral vascular function has not been reported. We have suggested in isolated porcine cerebral arteries that ₇-nicotinic acetylcholine receptors (₇-nAChRs) on perivascular sympathetic nerves mediate calcium influx in these neurons, resulting in release of norepinephrine. The released norepinephrine then acts on presynaptic ₂-adrenoceptors located on the neighboring nitrergic nerve terminals, causing nitric oxide (NO) release and vasodilation. Because Pb²⁺ has been shown to inhibit ₇-nAChR-mediated responses in the central nervous system, effects of Pb²⁺ on ₇-nAChR-mediated nitrergic neurogenic dilation in isolated porcine basilar arteries and calcium influx in cultured superior cervical ganglion (SCG) cells of the pig were examined using in vitro tissue bath and confocal microscopic techniques. The results indicated that Pb²⁺ (but not Cd²⁺, Zn²⁺, or Al³⁺) in a concentration-dependent manner blocked relaxation of endothelium-denuded basilar arterial rings induced by nicotine (100 µM) and choline (1 mM) without affecting relaxation induced by sodium nitroprusside or isoproterenol. Furthermore, significant calcium influx in cultured SCG cells induced by choline and nicotine was attenuated specifically by Pb²⁺ with IC₅₀ values comparable with those from tissue bath study. These results provide evidence supporting that lead is a likely antagonist for ₇-nAChRs that are found on postganglionic sympathetic adrenergic nerve terminals of SCG origin. Furthermore, these results indicate that lead can attenuate dilation of cerebral arteries by blocking sympathetic nerve-mediated release of NO from the perivascular nitrergic nerves.

Address correspondence to: Dr. Tony J.-F. Lee, Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629. E-mail: tlee{at}siumed.edu or tlee{at}mail.tcu.edu.tw

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