Positive inotropic activity exerted by the montelukast-androsterone derivative in a model of congestive heart failure (CHF)

Several studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the androsterone derivatives at cardiovascular level. Therefore, in this study, the inotropic activity of montelukast-androsterone was evaluated using an isolated rat heart model. In the first stage, the Langendorff technique was used to measure perfusion pressure and coronary resistance changes in isolated rat heart in absence or presence of androsterone and its derivative. In second stage, the inotropic activity of montelukast-androsterone was evaluated by measuring left ventricular pressure (LVP) in absence or presence of the following compounds; flutamide, prazosin, metoprolol, nifedipine and carbachol. The results showed that the montelukast-androsterone derivative significantly increase the perfusion pressure and coronary resistance in comparison with androsterone and control conditions. In addition, other data indicate that montelukast-androsterone derivative increase LVP in a dose-dependent manner [1 × 10-9 to 1 × 10-4 mmol]; nevertheless, this phenomenon was significantly inhibited by flutamide at a dose of 1 × 10-6mmol. Finally, other data indicate that the effect exerted by androsterone derivative [1 × 10-7 to 1 × 10-4 mmol] on LVP was blocked in the presence of carbachol [1 × 10-3 mmol]. All these data suggest that the montelukast-androsterone derivative induces positive inotropic activity through activation of the androgen receptor. In addition, this phenomenon may involvechanges on the cAMP concentration.   Key words: Montelukast-androsterone derivative, Langendorff, inotropic activity.