Gender-specific hypertension and responsiveness to nitric oxide in sGCα1 knockout mice

摘要: Aim The effects of nitric oxide (NO) in the cardiovascular system are attributed part to cGMP synthesis by α1β1 isoform soluble guanylate cyclase (sGC). Because available sGC inhibitors neither enzyme- nor isoform-specific, we generated knockout mice for α1 subunit (sGCα1−/− mice) order investigate function sGCα1β1 regulation blood pressure and cardiac function. Methods results Blood was evaluated, using both non-invasive invasive haemodynamic techniques, intact gonadectomized male female sGCα1−/− wild-type (WT) mice. Cardiac assessed with a conductance catheter inserted left ventricle WT Male developed hypertension (147 ± 2 mmHg), whereas did not (115 mmHg). Orchidectomy treatment an androgen receptor antagonist prevented hypertension, while ovariectomy influence phenotype. Chronic testosterone increased ovariectomized but NO synthase inhibitor N ω -nitro-L-arginine methyl ester hydrochloride raised similarly ability donor compounds reduce slightly attenuated as compared direct stimulator BAY 41-2272 reduced only Increased contractility arterial elastance well impaired ventricular relaxation were observed mice. Conclusion These findings demonstrate that sGCα1β1-derived signalling has gender-specific testosterone-dependent reveal on systemic do require sGCα1β1.