POSITIVE INOTROPIC EFFECT OF ANGIOTENSIN-II - INCREASES IN INTRACELLULAR CA2+ OR CHANGES IN MYOFILAMENT CA2+ RESPONSIVENESS

Although it is well known that Angiotensin II (Ang II) has a direct po sitive inotropic effect in several species, the mechanisms of this act ion are still poorly understood. The aim of this review is to analyze the possible subcellular mechanisms underlying Ang II-induced positive inotropic action. The binding of Ang II to its receptor triggers a co mplex signal transduction cascade that stimulates the intracellular fo rmation of two second messengers, inositol 1,4,5-triphosphate (IP3), a nd 1,2, diacylglycerol (DAG). IP3 triggers the release of Ca2+ from in tracellular stores in several cell types and has been shown to increas e myofilament Ca2+ sensitivity. DAG activates protein kinase C (PKC), an enzyme that catalyzes the phosphorylation of different cellular pro teins, including several proteins of the myofibrils. Distinct ionic tr ansporters, like the Na+/H+ antiporter and the Na+-independent Cl-/HCO 3- exchanger, implicated in the regulation of intracellular pH, and th e Na+/Ca2+ exchanger which contribute to the intracellular Ca2+ homeos tasis, have been shown to be activated by a PKC-dependent mechanism. T hus, either one of the Ang II-induced second messengers, that is, IP3 and DAG, has the potential to affect myocardial contractility by modif ying either intracellular Ca2+, myofilament Ca2+ responsiveness, or bo th. As described herein, the available data do not allow a definitive single model to explain the mechanism of the Ang II-induced positive i notropic effect. Moreover, it is possible that the final action of Ang II on myocardial inotropism is the end product of a complex interacti on of several of the mechanisms triggered by the hormone. (C) 1997 Els evier Science Inc.