CA2-RAT CARDIOMYOCYTES BY ANGIOTENSIN TYPE-1 AND TYPE-2 RECEPTORS( MOBILIZATION IN ADULT)

The role of angiotensin II (AngII) in the regulation of heart function under normal and pathological conditions has been well documented. Al though two types of AngII receptors (AT(1) and AT(2) receptors) are fo und in equal proportions in the rat heart, most studies have focused p rimarily on AT(1) receptor-coupled events. In this study, the contribu tion of both types of AngII receptors to cardiac function was evaluate d by measuring intracellular calcium ([Ca2+](i)) levels at ambient tem perature in freshly isolated adult rat ventricular cardiomyocytes. Exp osure of cardiomyocytes to AngII (0.01 to 10 mu M) resulted in an imme diate and sustained increase in [Ca2+](i) in a concentration-dependent manner. The increase in [Ca2+](i) in cardiomyocytes by AngII was bloc ked by either losartan or compound PD123319 -tetrahydro-1H-imidazo[4,5 -c]pyridine-6-carboxylic acid), non-peptide antagonists of the AT(1) a nd AT(2) receptors, respectively. The specificity of the action of the se antagonists was verified by their inability to alter the basal leve ls of [Ca2+](i) as well as KCl- or ATP-induced increases in [Ca2+](i). AngII was also observed to initiate spontaneous beating activity in c ardiomyocytes, which was prevented by both losartan and compound PD123 319 in a concentration dependent manner (0.01 to 10 mu M). These data indicate that the activation of both AT(1) and AT(2) receptors may sti mulate a signalling pathway that influences [Ca2+](i) and spontaneous beating activity in cardiomyocytes. (C) 1998 Elsevier Science Inc.