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(Hypertension. 1997;30:1253-1259.)
© 1997 American Heart Association, Inc.

Articles

Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats

Jeannette Fareh; Rhian M. Touyz; Ernesto L. Schiffrin; Gaetan Thibault

From the Medical Research Council Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal (Quebec, Canada).

Correspondence to Gaetan Thibault, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7. Email thibaug{at}ircm.umontreal.ca

Abstract 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 acetate (DOCA)–salt and control unilaterally nephrectomized (Uni-Nx) Sprague-Dawley rats was assessed. Ang II receptor density and intracellular Ca²⁺ concentration measurements were examined in adult ventricular myocytes and fibroblasts by radioligand binding assay and digital imaging using fura 2 methodology, respectively. Four-week DOCA-salt treatment induced hypertension associated with cardiac hypertrophy. Ang II binding studies demonstrated that adult ventricular myocytes and fibroblasts possess mainly the AT₁ subtype receptor. Moreover, DOCA-salt hypertension was associated with a 1.8-fold increase in Ang II–specific binding 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 frequency were unaltered in cardiomyocytes from DOCA-salt–hypertensive rats. The density of AT₁ subtype receptors was not modified in ventricular fibroblasts after DOCA-salt treatment. Ang II increased intracellular Ca²⁺ concentration similarly in ventricular fibroblasts from normal and hypertensive rats. In conclusion, DOCA-salt hypertension is characterized by an increased AT₁ receptor density and intracellular calcium responses in ventricular myocytes, whereas in ventricular fibroblasts the AT₁ receptor status is unaltered. These findings report for the first time the cardiac cell–specific implication of Ang II and the intracellular calcium signaling pathway stimulated by the AT₁ receptor in cardiac hypertrophy in DOCA-salt–hypertensive rats.

Key Words: hypertrophy • myocytes • fibroblasts • calcium

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