Design and synthesis of an estradiol derivative and evaluation of its inotropic activity in isolated rat heart

摘要

Several studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the estradiol derivatives at cardiovascular level. Therefore, in this study, estradiol derivative was synthetized with the objective of evaluating its inotropic activity. In this first stage, the Langendorff technique was used to measure perfusion pressure and coronary resistance changes in isolated rat heart in absence or presence of estradiol derivative. In second stage, the inotropic activity of estradiol derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine.?The results showed that the estradiol derivative significantly increase the perfusion pressure and coronary resistance in isolated heart. Additionally, other data indicate that estradiol derivative increaseleft ventricular pressure?in a dose-dependent manner [10-9?to 10-4?mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1?× 10-6?mmol. In conclusion, these data suggest that the estradiol derivative induces positive inotropic activity through of activation the L-type calcium channel.