Evaluation of Positive Inotropic Activity Induced bya Danazol Derivative in Isolated Rat Heart Model

Abstract

<span style="font-family:Verdana;">T</span><span style="font-family:Verdana;">here is scarce information about the effects of </span><span><span style="font-family:Verdana;">danazol and its </span><span style="font-family:Verdana;">derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of </span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> at the cardiovascular level is very confusing. In order</span></span><span> </span><span style="font-family:Verdana;">to clarify those phenomena in this study, a </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> derivative was synthesized with the objective of</span></span><span> </span><span style="font-family:Verdana;">evaluat</span><span style="font-family:Verdana;">ing</span><span style="font-family:Verdana;"> its activity on per</span><span style="font-family:Verdana;">fusion pressure and coronary resistance and compar</span><span style="font-family:Verdana;">ing</span><span style="font-family:Verdana;"> this phenomenon with the effect exerted by </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;">. </span><span style="font-family:Verdana;">T</span><span style="font-family:Verdana;">he Lan</span></span><span style="font-family:Verdana;">gendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by </span><span style="font-family:Verdana;">danazol </span><span style="font-family:Verdana;">derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds; flutamide, prazosin, metoprolol, indomethacin and nifedipine.</span></span><span> </span><span style="font-family:Verdana;">The results showed that </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> derivative significantly increased the perfusion pressure and coronary resistance in com</span></span><span style="font-family:Verdana;">parison with the control conditions and </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;">. Additionally, other data indicate that the</span></span><span> </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> derivative increase</span></span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> left ventricular pressure in a dose-dependent manner; nevertheless, this phenomenon was significantly inhibited by flu</span><span style="font-family:Verdana;">tamide. These data suggest that </span><span><span style="font-family:Verdana;">danazol</span><span style="font-family:Verdana;"> derivative induces positive in...

Design and synthesis of new dihydrotestosterone derivative with positive inotropic activity

“…iii = cupric chloride anhydrous/rt. acid) shown positive inotropic activity via L-type calcium channel activation in an isolated rat heart model [11]. In addition, there data which indicate that some androgens also exert cardiotonic effects, for example, there is a study which indicate that the androgen derivative (E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione Hydrochloride induce positive inotropic effect in guinea pig atria is via inhibition of Na+, K (+)-ATPase [12].…”