Estrogen prevents β-amyloid inhibition of sympathetic α7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries

Authors

  • M.-L. Si,

    1.  Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA
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  • C. Long,

    1.  College of Life Science, South China Normal University, Guangzhou, China
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  • M.-F. Chen,

    1.  Department of research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
    2.  Tzu Chi College of Technology, Hualien, Taiwan
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  • T. J.-F. Lee

    1.  Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA
    2.  Department of Life Sciences, College of Life Sciences, Tzu Chi University, Hualien, Taiwan
    3.  Tzu Chi Center for Vascular Medicine, Tzu Chi University, Hualien, Taiwan
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Dr. T. J.-F. Lee, College of Life Sciences, Tzu Chi University, Hualien, Taiwan.
E-mail: tlee@mail.tcu.edu.tw; tlee@siumed.edu

Abstract

Aim:  β-amyloid peptides (Aβs) have been shown to block cerebral nitrergic neurogenic vasodilation by blocking sympathetic α7-nAChRs, and that oestrogen prevents Aβ-induced neurotoxicity. We examined whether Aβ-inhibition of α7-nAChR-mediated cerebral nitrergic vasodilation was prevented by oestrogen.

Methods:  Effects of Aβ and 17β-oestradiol on neurogenic nitrergic vasodilation in isolated porcine basilar arteries were examined using wire-myography. Drug effects on nicotine- and choline-induced calcium influx and inward currents in porcine cultured superior cervical ganglion (SCG) were investigated using confocal microscopy and patch-clamp techniques respectively.

Results:  Precontracted endothelium-denuded basilar arteries relaxed exclusively upon transmural nerve stimulation (TNS, 8 Hz), and applications of nicotine (100 μm) or choline (1 mm), which was sensitive to nitro-L-arginine (L-NNA, 30 μm) and tetrodotoxin (0.3 μm). The relaxation induced by nicotine and choline but not that by TNS was blocked reversibly by Aβ1-40 in a concentration-dependent manner. Aβ1-40 also reversibly blocked nicotine- and choline-induced increase of calcium influx and inward currents in the SCG neurons. Aβ inhibition of nicotine- and choline-induced α7-nAChR-mediated nitrergic vasodilation and inward currents was prevented by 17β-oestradiol (10 μm), but not by α-oestradiol (10 μm) or testosterone (10 μm).

Conclusion:  These results provide further evidence supporting that Aβ is an antagonist for the α7-nAChR found on post-ganglionic sympathetic adrenergic nerve terminals originating in the SCG. Aβ can cause constriction of cerebral arteries with possible decreased regional cerebral blood flow by blocking sympathetic nerve-mediated release of nitric oxide from the perivascular nitrergic nerves. This effect of Aβ can be prevented by endogenous oestrogen but not testosterone.

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