title: Estrogen prevents β-amyloid inhibition of sympathetic α7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries.
abstract: OBJECTIVE
  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 Aβ(1-40) in a concentration-dependent manner. Aβ(1-40) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, USA.
authors.forename: M-L
authors.initials: ML
authors.lastname: Si
authors.forename: C
authors.initials: C
authors.lastname: Long
authors.forename: M-F
authors.initials: MF
authors.lastname: Chen
authors.forename: T J-F
authors.initials: TJ
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008297:Male; D018613:Microscopy, Confocal; D026602:Nitrergic Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D016229:Amyloid beta-Peptides; D004967:Estrogens; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D004958:Estradiol