eNOS phosphorylation and translocation are altered in male but not female mice by increased activation of the Gαq protein

Little is known about sex-dependent physiological and pathophysiological differences in cardiac endothelial nitric oxide synthase (eNOS) expression and activation. Therefore, we investigated cardiac morphology and eNOS protein expression, including its translocation-dependent activation and phosphorylation, in cardiac tissue of male and female wild-type mice and transgenic heart-failure mice having a cardiac-specific, 5-fold overexpression of the G alpha(q) protein. In addition, we measured calcineurin protein expression. Heart-to-body weight ratio was increased in G alpha(q) mice. Female wildtype mice showed higher eNOS protein expression and activation (translocation and phosphorylation) than did wild-type males. In cardiac tissue of G alpha(q) mice, these sex-dependent differences remained or were enhanced. Protein expression of the catalytic subunit calcineurin A, which has been shown to dephosphorylate eNOS, was higher in wild-type males than in wild-type females. These differences were increased in the G alpha(q) mice model. We conclude that sex differences exist in cardiac eNOS protein expression and phosphorylation. Increased activation of the G alpha(q) protein appears to alter eNOS protein expression and phosphorylation only in males.