Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.

摘要: Nitric oxide (NO), constitutively produced by endothelial nitric synthase (eNOS), plays a major role in the regulation of blood pressure and vascular tone. We generated transgenic mice overexpressing bovine eNOS wall using murine preproendothelin-1 promoter. In lineages with three to eight transgene copies, eNOS-specific mRNA, protein expression particulate fractions, calcium-dependent NOS activity were confirmed RNase protection assay, immunoblotting, L-arginine/citrulline conversion. Immunohistochemical studies revealed that was predominantly localized cells aorta, heart, lung. Blood significantly lower eNOS-overexpressing than control littermates. basal NO release (estimated Nomega-nitro-L-arginine-induced facilitation contraction prostaglandin F2alpha) cGMP levels (measured enzyme immunoassay) increased. contrast, relaxations aorta response acetylcholine sodium nitroprusside attenuated, reduced reactivity associated elevation these agents as compared aortas. Thus, our novel mouse model chronic overexpression demonstrates that, addition essential regulation, tonic endothelium induces NO-mediated vasodilators, providing several insights into pathogenesis nitrate tolerance.