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

L. Figueroa-Valverde, Figueroa‐Valverde Lauro, Francisco Díaz-Cedillo, E. García-Cervera, García-Cervera Elodia, Eduardo Pool Gómez, María López-Ramos, Rosas‐Nexticapa Marcela, M. Rosas-Nexticapa, Ma. Remedios Mendoza-López, I. May-Gil, A. Sarao'
In: Pharmacology & Pharmacy · 2013 · vol. 04(04) , pp. 406–415 · doi:10.4236/pp.2013.44058 · W2089001217
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A synthesized danazol derivative increased perfusion pressure, coronary resistance, and left ventricular pressure in isolated rat hearts, primarily via androgen receptor activation.

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Abstract

There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confusing. In order to clarify those phenomena in this study, a danazol derivative was synthesized with the objective of evaluating its activity on perfusion pressure and coronary resistance and comparing this phenomenon with the effect exerted by danazol. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of danazol and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by danazol derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds; flutamide, prazosin, metoprolol, indomethacin and nifedipine. The results showed that danazol derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and danazol. Additionally, other data indicate that the danazol derivative increases left ventricular pressure in a dose-dependent manner; nevertheless, this phenomenon was significantly inhibited by flutamide. These data suggest that danazol derivative induces positive inotropic activity through of the activation androgen receptor.

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