Ca2+ mobilization in adult rat cardiomyocytes by angiotensin type 1 and 2 receptors

The role of angiotensin II (AngII) in the regulation of heart function under normal and pathological conditions has been well documented. Although two types of AngII receptors (AT1 and AT2 receptors) are found in equal proportions in the rat heart, most studies have focused primarily on AT1 receptor-coupled events. In this study, the contribution of both types of AngII receptors to cardiac function was evaluated by measuring intracellular calcium ([Ca2+]i) levels at ambient temperature in freshly isolated adult rat ventricular cardiomyocytes. Exposure of cardiomyocytes to AngII (0.01 to 10 microM) resulted in an immediate and sustained increase in [Ca2+]i in a concentration-dependent manner. The increase in [Ca2+]i in cardiomyocytes by AngII was blocked by either losartan or compound PD123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid), non-peptide antagonists of the AT1 and AT2 receptors, respectively. The specificity of the action of these antagonists was verified by their inability to alter the basal levels of [Ca2+]i as well as KCl- or ATP-induced increases in [Ca2+]i. AngII was also observed to initiate spontaneous beating activity in cardiomyocytes, which was prevented by both losartan and compound PD123319 in a concentration-dependent manner (0.01 to 10 microM). These data indicate that the activation of both AT1 and AT2 receptors may stimulate a signalling pathway that influences [Ca2+]i and spontaneous beating activity in cardiomyocytes.