Key result
In ovariectomized rats with pressure overload, 17β-estradiol prevented the 20% greater decline in cardiac performance seen with placebo (P<0.015) and regulated NOS3 activity.
Why the study?
Does 17β-estradiol improve cardiac function and regulate NOS expression in rats with pressure overload-induced cardiac hypertrophy?
Does 17β-estradiol improve cardiac function and regulate NOS expression in rats with pressure overload-induced cardiac hypertrophy?
In a rat model of pressure overload, 17β-estradiol preserves cardiac function by regulating NOS3 activity, whereas pressure overload independently induces NOS1 expression.
Suggests estradiol may preserve function via NOS3 in estrogen-deficient rat models; leaves open translation to human postmenopausal heart failure.
Estrogens [E(2)] exert direct and indirect effects that can modulate the development of cardiac disease. However, the precise mechanisms that are involved remain undefined. Our objective was to investigate whether E(2) affected the activity and expression of constitutive nitric oxide synthase (NOS) isoforms (NOS3 and NOS1) in cardiac hypertrophy induced by thoracic aortic constriction (TAC). Ovariectomized (Ovx) and nonovariectomized Wistar rats were subjected to TAC. Ovx animals received E(2) or placebo 3 wk after surgery for 11 wk. Afterward cardiac function and degree of left ventricular hypertrophy were assessed by echocardiography. NOS activity and expression were studied by biochemical techniques. TAC led to significant left ventricular hypertrophy (>90%) irrespective of hormonal status. Cardiac performance declined more in TAC+Ovx (-20%, P < 0.015) than in the two other TAC groups [TAC and TAC+Ovx+E(2)]. Total NOS activity decreased significantly in the Ovx groups. In response to TAC, total NOS activity increased whatever the E(2) status. Specific NOS3 activity dramatically decreased in the Ovx groups (-55%, P < 0.009) and was unaltered by TAC. By using coimmunoprecipitation assays, we showed that NOS3/caveolin-1 complexes negatively regulated NOS3 activity as a function of E(2) status. On the other hand, NOS1 expression and activity were markedly increased in hypertrophied myocardium (P < 0.003), irrespective of E(2) status. This study demonstrates a differential regulation of NOS expression and activity in response to pressure overload and E(2) status, the former being mainly involved in the induction of NOS1, whereas the latter regulated NOS3 activity and in turn cardiac function.
No takes yet. Share an insight, caveat, or question.
Loyer et al. (2007) studied Cardiac hypertrophy induced by thoracic aortic constriction. 17β-Estradiol vs. Placebo was evaluated on Cardiac performance and NOS activity (p=<0.015). In ovariectomized rats with pressure overload, 17β-estradiol prevented the 20% greater decline in cardiac performance seen with placebo (P<0.015) and regulated NOS3 activity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:
More on Hypertension managementMore from Endocrinology