Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model
Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model
L. Figueroa-Valverde(the University Autonomic of Campeche); F. Dı´az-Cedillo(Polite´cnico Nacional); E. Garcı´a-Cervera(the University Autonomic of Campeche); E. Pool Go´mez(the University Autonomic of Campeche); M. Lo´pez-Ramos(the University Autonomic of Campeche); M. Rosas-Nexticapa(Universidad Veracruzana); R. Martinez-Camacho(Instituto tecnolo´gico de la Paz)
36권 10호, 1270~1278쪽
초록
Experimental studies indicate that some steroidderivatives have inotropic activity; nevertheless, there isscarce information about the effects of the dehydroisoandrosteroneand its derivatives at cardiovascular level. Inaddition, to date the cellular site and mechanism of actionof dehydroisoandrosterone at cardiovascular level is veryconfusing. In order, to clarify those phenomena in this study,a dehydroisoandrosterone derivative was synthesized withthe objective of to evaluate its activity on perfusion pressureand coronary resistance and compare this phenomenon withthe effect exerted by dehydroisoandrosterone. The Langendorfftechnique was used to measure changes on perfusionpressure and coronary resistance in an isolated rat heartmodel in absence or presence of dehydroisoandrosterone andits derivative. Additionally, to characterize the molecularmechanism involved in the inotropic activity induced bydehydroisoandrosterone derivative was evaluated by measuringleft ventricular pressure in absence or presence offollowing compounds; flutamide, prazosin, metoprolol andnifedipine. The results showed that dehydroisoandrosteronederivative significantly increased the perfusion pressure andcoronary resistance in comparison with the control conditionsand dehydroisoandrosterone. Additionally, other dataindicate that dehydroisoandrosterone derivative increase leftventricular pressure in a dose-dependent manner [1 9 10-9–1 9 10-4 mmol]; nevertheless, this phenomenon was significantlyinhibited by nifedipine at a dose of 1 9 10-6mmol. In conclusion, these data suggest that dehydroisoandrosteronederivative induces positive inotropic activitythrough of activation the L-type calcium channel.
Abstract
Experimental studies indicate that some steroidderivatives have inotropic activity; nevertheless, there isscarce information about the effects of the dehydroisoandrosteroneand its derivatives at cardiovascular level. Inaddition, to date the cellular site and mechanism of actionof dehydroisoandrosterone at cardiovascular level is veryconfusing. In order, to clarify those phenomena in this study,a dehydroisoandrosterone derivative was synthesized withthe objective of to evaluate its activity on perfusion pressureand coronary resistance and compare this phenomenon withthe effect exerted by dehydroisoandrosterone. The Langendorfftechnique was used to measure changes on perfusionpressure and coronary resistance in an isolated rat heartmodel in absence or presence of dehydroisoandrosterone andits derivative. Additionally, to characterize the molecularmechanism involved in the inotropic activity induced bydehydroisoandrosterone derivative was evaluated by measuringleft ventricular pressure in absence or presence offollowing compounds; flutamide, prazosin, metoprolol andnifedipine. The results showed that dehydroisoandrosteronederivative significantly increased the perfusion pressure andcoronary resistance in comparison with the control conditionsand dehydroisoandrosterone. Additionally, other dataindicate that dehydroisoandrosterone derivative increase leftventricular pressure in a dose-dependent manner [1 9 10-9–1 9 10-4 mmol]; nevertheless, this phenomenon was significantlyinhibited by nifedipine at a dose of 1 9 10-6mmol. In conclusion, these data suggest that dehydroisoandrosteronederivative induces positive inotropic activitythrough of activation the L-type calcium channel.
- 발행기관:
- 대한약학회
- 분류:
- 약학