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

摘要

There are studies which indicate that some fluorobenzene derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. To clarify these phenomena in this study, a new fluorobenzene derivative was synthesized to evaluate its biological activity on perfusion pressure and left ventricular pressure. 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 the fluorobenzene derivative [0.001 nM]. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the fluorobenzene derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; ouabain, digoxin, levosimendan, cyclopiazonic acid and thapsigargin. The results showed that the fluorobenzene derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that fluorobenzene derivative increase perfusion pressure in a form similar to ouabain and digoxin; however, this effect was different compared with levosimendan. Other results showed that biological activity induced by the fluorobenzene on left ventricular pressure was significantly inhibited by both cyclopiazonic acid [50 mM] and thapsigargin [300 mM]. These data suggest that positive inotropic activity induced by the fluorobenzene on perfusion pressure and left ventricular pressure was via changes of biological activity both Na,K-ATPase and Ca~(+2)-ATPase. This phenomenon is a particularly interesting because the positive inotropic activity induced by this fluorobenzene derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.