Angiotensin II and cardiac excitation-contraction coupling: questions and controversies.
Angiotensin II (AngII) is a circulating peptide that produces a positive inotropic effect in the heart in several species, including humans. The subcellular mechanisms involved in producing this effect have been the focus of numerous studies; however, the results of these studies have generated considerable controversy. Although part of the controversy might arise from species and developmental differences, conflicting results have also been reported in the same species. To further complicate the understanding of the cardiac actions of AngII, the binding of the peptide to its transmembrane G-protein-coupled receptors has been shown to activate signalling cascades that involve numerous second messengers. Among these, inositol 1,4,5-triphosphate (IP3) and protein kinase C (PKC) have been shown to have the potential to modulate either one or both of the two basic mechanisms known to increase contractility: (i) an increase in the intracellular Ca2+ concentration ([Ca2+]i); or (ii) an increase in myofilament responsiveness to Ca2+. The aim of this review is to examine the effect of AngII on the fundamental components of cardiac excitation-contraction coupling: calcium currents, Na+/Ca2+ exchange, sarcoplasmic reticulum (SR)-CaZ+ release, calcium transients and contractile proteins. An answer to the following question is sought: Is the positive inotropic effect of AngII due to an increase in [Ca2+]i, to an increase in myofilament responsiveness to Ca2+, or to both?
Vila Petroff
M G
MG
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina. mvila@atlas.med.unlp.edu.ar
Mattiazzi
A R
AR