Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes

Isolated calcium-tolerant rat ventricular cardiomyocytes were used to characterize the effects of atrial natriuretic peptide (ANP), Angiotensin II (AII) and their interaction on the myocardial contraction-/relaxation pattern free of interference from other types of cardiac cells. Binding of 125I-ANP showed a KD of 12 pM and approximately 600 binding sites per cell. At 37 degrees C (rate 140 bpm) ANP decreased the contraction maximum with an EC50 of about 70 pM, maximal decrease was 35%. ANP (10(-7) M) raised cellular cyclic-GMP from 0.76+/-0.12 to 1.32+/-0.13 pmole/10(6) cells (73%, p less than 0.05). Angiotensin II increased contractility by a maximum of 32% at 10(-7) M; the EC50 was 8 x 10(-10) M. AII markedly delayed relaxation (reduction of maximum relaxation velocity from 0.092 to 0.063 mm/s; p less than 0.05). ANP (10(-7) M) increased the effect of AII (10(-8) M) on contractility by 66% without changing relaxation parameters significantly. This unexpected interaction may be relevant in pathological conditions where both AII and ANP are stimulated, such as heart failure or secondary hypertension.