Estrogen-induced endothelial alterations in endothelial nitric oxide synthase (eNOS) may contribute to the gender-differences in cardiovascular disease. We investigated cardiac morphology, eNOS translocation and ?phosphorylation, oxidative/nitrosative stress, and calcineurin protein expression in hearts of male and female wildtype (WTM , WTF ) and transgenic mice with a 5-fold overexpression of the Gaq-protein (GaqM , GaqF ).

Heart-to-body weight ratio, endsystolic and -diastolic diameter were increased in Gaq-animals. ENOS protein expression, - translocation and phosphoryation (Ser1177, Ser116, Ser635) were significantly increased in WTF compared to WTM but unaltered in GaqF compared to WTF . eNOS-protein and eNOSSer635- phosphorylation were increased, phospho-eNOSSer1177 was decreased, and eNOS-translocation and phospho-eNOSSer116 unaltered in GaqM compared to WTM . Calcineurin A-protein expression was increased in WTM compared to WTF and increased in GaqM compared to WTM but decreased in GaqF compared to WTF .

Conclusions: Gender-differences exist in cardiac eNOS protein expression and ?activation. Gaq-protein activation alters eNOS-activation only in male gender. These altertions may be partly responsible for an accelerated decline of cardiac tissue in male gender.