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.
Neyses
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Department of Medicine, University of Bonn, Federal Republic of Germany.
Vetter
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H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016276:Ventricular Function
D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP