Effects of a nonpeptide angiotensin II receptor antagonist (CV-11974) on [Ca²⁺]_i and cell motion in cultured ventricular myocytes

We studied the effects of angiotensin II and CV-11974 (a newly synthesized angiotensin II receptor antagonist) on cell contraction and [Ca²⁺]_i in cultured neonatal rat ventricular myocytes. Exposure of these cells to 10 nM angiotensin II significantly decreased peak systolic cell position (60.1±3.3% of the control, P < 0.01) and peak systolic [Ca²⁺]_i (from 1111 ± 250 to 572 ± 143 nM, P < 0.05) within 60 s. Pretreatment of ventricular myocytes with CV-11974 (10-100 nM) completely suppressed the angiotensin II-induced changes in peak systolic cell position and [Ca²⁺]_i. These results suggest that CV-11974 inhibits cardiac angiotensin II receptors.