Activity induced by a progesterone derivative on injury by ischemia-reperfusion in an isolated heart model

Several studies indicate that some steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the effects of progesterone and its derivatives on cardiac injury ischemia/reperfusion (I/R). Therefore, in this study, a progesterone derivative was evaluated 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 progesterone derivative on perfusion pressure and coronary resistance was assed using the Langendorff technique by measuring left ventricular pressure in the absence or presence of mifepristone, yohimbine, ICI 118,551, atropine, methoctramine and L-NG-nittroarginine methyl esther (L-NAME). The results showed that progesterone derivative reduced infarct size compared with progesterone and control. In addition, it was also observed that the progesterone derivative significantly decreased the perfusion pressure and coronary resistance in isolated heart. Additionally, another set of data indicate that progesterone derivative produces low left ventricular pressure in a dose-dependent manner [0.001 to 100 nM]; however, this phenomenon was significantly inhibited by methoctramine (1 nM) and L-NAME (1 nM). In conclusion, these data suggest that a cardioprotective effect of progesterone derivative is through the interaction with M2 muscarinic and activation of nitric oxide synthase which may be responsible for the reduction in myocardial necrosis after ischemia and reperfusion.   Key words. Progesterone derivative, ischemia/reperfusion, methoctramine and L-NG-nittroarginine methyl esther (L-NAME).