Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model

Abstract

Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 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 dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

Design and Synthesis of a New Androgen Derivative using Some Strategies

“…The second stage was achieved by reaction of the compound 3 with testosterone ( Figure 2) resulting in imino bond formation involved in the compound 5(10,13-Dimethyl-3-{2-[( [1,10]phenanthrolin-5-ylmethyl)-amino]-ethylimino}-2,3,6,7,8,9,10,11,12,13,14,15,16, 17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol).It is notewor thy thatthere are several proceduresfor the synthesisofiminogroups are previously described intheliterature [13][14][15] ; for example the synthesis of a steroid derivative by the reaction of N 1 -(2,3-dimethoxystrychnidin-10-yliden)-ethane-1,2-diamine with a steroid derivative using boric acid as catalyst 4 . For this reason, in this study this reagent was used as catalyst in the reaction of the compound 3 with testosterone ( Figure 1) to form the compound 5.The 1 H NMR spectrum of 5 shows signals at 0.80 and 1.02 ppm for methyl groups; at 0.92-1.00, 1.06-2.38, 3.68 and 5.90 ppm for steroid nucleus; at 3.04 and 3.50 ppm for methylene groups bound to both imino and amino groups; at 4.10 ppm for methylene group bound to both phenyl and amino groups; at 4.70 ppm for both amino and hydroxyl groups; at 7.00-7.80 for phenanthroline fragment.…”

“…In addition, other study showed the synthesis of (17S)-spiro-3,3-(dimethoxy)-5-androstan-17,2´-oxirane by the reaction of 3,3-(dimethoxy)-5-androstan-17-one with trimethylsulfonium iodide in DMF 3 . There is other reportwhich shown the synthesis of the dehydroisoandrosterone derivative by the reaction between a brucine derivative anddehydroiso androsterone 3-sulfate using boric acid as catalyst 4 .…”

Evaluation of Inotropic Activity of Fluorobenzene Derivative Using an Isolated Rat Heart Model

“…ionic channels or specific receptors) involved in the endothelium of coronary artery; or 3) possibly by the influence exerted by the compound 3 on blood pressure which results as a reduction in the infarct size, and decrease the myocardial injury after ischemia-reperfusion. Analyzing this hypothesis and other reports [35,36] which indicate that some compounds reduce the infarct area by induce changes on perfusion pressure; in this study, the biological activity of compounds 2,4-dinitrofluorobenzene, 2 and 3 on perfusion pressure was evaluated in an isolated rat heart model. The results show that only the compound 3 significantly increases the perfusion pressure over time compared with compounds 2,4-dinitrofluorobenzene, or 2 and the control conditions.…”

Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

“…Analyzing the results obtained and other reports which indicate that some steroid derivatives can induce changes on blood pressure by increasing calcium levels [42]; in this study, we also considered validating the effect induced by the testosterone derivative on left ventricular pressure via the calcium channels activation using as pharmacological tool to nifedipine. The results showed that the effect induced by the testosterone derivative was not inhibited in the presence of nifedipine.…”