Estrogen prevents beta -amyloid inhibition of sympathetic alpha 7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries

• Published in: Acta Physiologica Vol. 203; no. 1; pp. 13 - 23
• Main Authors: Si, M-L, Long, C, Chen, M-F, Lee, TJ-F
• Format: Journal Article
• Language: English
• Published: 01-09-2011
• Subjects: Adrenergic nerves; Alzheimer's disease; Arteries; beta -Amyloid; Calcium influx; Cerebral blood flow; Choline; Confocal microscopy; Drugs; Estrogens; Neurons; Neurotoxicity; Nicotine; Nitric oxide; superior cervical ganglion; Testosterone; Tetrodotoxin; Vasodilation
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2010.02224.x

Aim: beta -amyloid peptides (A beta s) have been shown to block cerebral nitrergic neurogenic vasodilation by blocking sympathetic alpha 7-nAChRs, and that oestrogen prevents A beta -induced neurotoxicity. We examined whether A beta -inhibition of alpha 7-nAChR-mediated cerebral nitrergic vasodilation was prevented by oestrogen. Methods: Effects of A beta and 17 beta -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, 8Hz), and applications of nicotine (100 mu m) or choline (1mm), which was sensitive to nitro-L-arginine (L-NNA, 30 mu m) and tetrodotoxin (0.3 mu m). The relaxation induced by nicotine and choline but not that by TNS was blocked reversibly by A beta 1-40 in a concentration-dependent manner. A beta 1-40 also reversibly blocked nicotine- and choline-induced increase of calcium influx and inward currents in the SCG neurons. A beta inhibition of nicotine- and choline-induced alpha 7-nAChR-mediated nitrergic vasodilation and inward currents was prevented by 17 beta -oestradiol (10 mu m), but not by alpha -oestradiol (10 mu m) or testosterone (10 mu m). Conclusion: These results provide further evidence supporting that A beta is an antagonist for the alpha 7-nAChR found on post-ganglionic sympathetic adrenergic nerve terminals originating in the SCG. A beta 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 A beta can be prevented by endogenous oestrogen but not testosterone.