Susceptibility to cardiac ischemia/reperfusion injury modulated by an estrogen derivative

Abstract

Several studies indicate that some steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the effects of the estradiol derivatives on cardiac injury ischemia/reperfusion (I/R). Therefore, in this study, an estradiol derivative was synthetized with the objective of evaluating its activity on I/R in an ischemia-reperfusion model. In addition, molecular mechanism involved in the activity of effect induced by estradiol derivative on perfusion pressure and coronary resistance was evaluated using the Langendorff technique by measuring left ventricular pressure in absence or presence of the following compounds; tamoxifen, yohimbine, ICI 118,551 and L-NAME. The results showed that estradiol derivative reduced infarct size compared with control. In addition, another results showed that the estradiol derivative significantly decrease the perfusion pressure and coronary resistance in isolated heart. Additionally, another data indicate that estradiol derivative low left ventricular pressure in a dose-dependent manner (1 × 10-9 to 1 × 10-4 mmol); however, this phenomenon was significantly inhibited by tamoxifen at a dose of 1 × 10-6 mmol and L-NAME (1 × 10-6 mmol). In conclusion, these data suggest that cardioprotective effect of estradiol derivative is through the interaction with estrogen receptor and activation of nitric oxide synthase. This phenomenon results in decrease of myocardial necrosis after ischemia and reperfusion.