Abstract
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 α7-nicotinic acetylcholine receptors (α7-nAChRs) on perivascular sympathetic nerves mediate calcium influx in these neurons, resulting in release of norepinephrine. The released norepinephrine then acts on presynaptic β2-adrenoceptors located on the neighboring nitrergic nerve terminals, causing nitric oxide (NO) release and vasodilation. Because Pb2+ has been shown to inhibit α7-nAChR-mediated responses in the central nervous system, effects of Pb2+ on α7-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 α7-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.
Footnotes
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This work was supported by National Institutes of Health Grants HL27763 and HL47574, Tzu Chi Foundation (Taiwan, Japan), and Southern Illinois University-Central Research Committee/Excellence in Academic Medicine.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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DOI: 10.1124/jpet.102.046854.
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ABBREVIATIONS: NO, nitric oxide; SCG, superior cervical ganglion; nAChR, nicotinic acetylcholine receptors; TNS, transmural nerve stimulation; AM, acetoxymethyl ester; U046619, 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α
- Received November 22, 2002.
- Accepted February 25, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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