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.