CARDIAC TYPE-1 ANGIOTENSIN-II RECEPTOR STATUS IN DEOXYCORTICOSTERONE ACETATE-SALT HYPERTENSION IN RATS

The regulation of angiotensin II (Ang II) receptors and Ang II-induced modulation of intracellular Ca2+ concentration in cardiac cells from hearts of experimentally induced hypertensive deoxycorticosterone acet ate (DOCA)-salt and control unilaterally nephrectomized (Uni-Nx) Sprag ue-Dawley rats was assessed. Ang II receptor density and intracellular Ca2+ concentration measurements were examined in adult ventricular my ocytes and fibroblasts by radioligand binding assay and digital imagin g using fura 2 methodology, respectively. Four-week DOCA-salt treatmen t induced hypertension associated with cardiac hypertrophy. Ang II bin ding studies demonstrated that adult ventricular myocytes and fibrobla sts possess mainly the AT(1) subtype receptor. Moreover, DOCA-salt hyp ertension was associated with a 1.8-fold increase in Ang II-specific b inding compared with myocytes from Uni-Nx control rats. Intracellular Ca2+ responses induced by increasing Ang II concentrations (10(-12) to 10(-4) mol/L) were significantly enhanced in cardiomyocytes from DOCA -salt rats. The effects of Ang II on intracellular Ca2+ spike frequenc y were unaltered in cardiomyocytes from DOCA-salt-hypertensive rats. T he density of AT(1) subtype receptors was not modified in ventricular fibroblasts after DOCA-salt treatment. Ang II increased intracellular Ca2+ concentration similarly in ventricular fibroblasts from normal an d hypertensive rats. In conclusion, DOCA-salt hypertension is characte rized by an increased AT(1) receptor density and intracellular calcium responses in ventricular myocytes, whereas in ventricular fibroblasts the AT(1) receptor status is unaltered. These findings report for the first time the cardiac cell-specific implication of Ang II and the in tracellular calcium signaling pathway stimulated by the AT(1) receptor in cardiac hypertrophy in DOCA-salt-hypertensive rats.