ANGIOTENSIN-I AND ANGIOTENSIN-II EXERT INOTROPIC EFFECTS IN ATRIAL BUT NOT IN VENTRICULAR HUMAN MYOCARDIUM - AN IN-VITRO STUDY UNDER PHYSIOLOGICAL EXPERIMENTAL CONDITIONS

Background. The renin-angiotensin system with its renal-humoral and local myocardial components plays an important role in the development and progression of chronic heart failure. Whereas angiotensin receptors have been found in atrial and ventricular myocardium of different species including humans, its influence on myocardial contractility is not yet defined in human failing myocardium and especially in human nonfailing myocardium. Methods and Results. We measured force development of right atrial and right and left ventricular myocardial preparations of patients with a variety of cardiac diseases. To evaluate the physiological effects of angiotensin, experimental temperature and stimulation rates were 37-degrees-C and 60 beats per minute, respectively. Angiotensin I and II increased peak developed force in atrial myocardial preparations obtained from patients without heart failure in a concentration-dependent manner. At optimal concentrations, peak developed force is increased from 10.2+/-1.8 to 12.3+/-1.9 mN/mm2 by angiotensin I (P<.05) and from 15.4+/-2.1 to 20.5+/-3.3 mN/mm2 by angiotensin II (P<.05). This effect was not influenced by pretreatment with propranolol (10(-6) mol/L) and prazosin (10(-5) mol/L) but was completely blocked by saralasin (10(-6) mol/L). The positive inotropic effect of angiotensin I could be blocked by enalaprilate (10(-5) mol/L). Neither angiotensin I nor angiotensin II had any effect in preparations of the left ventricle from patients with idiopathic dilated cardiomyopathy, mitral valve stenosis, and incompetence or in patients with no significant heart disease. Additionally, no effect could be seen when angiotensin II was applied to right ventricular preparations from infants undergoing reconstructive heart surgery for tetralogy of Fallot. Conclusions. Angiotensin I and II exert positive inotropic effects via angiotensin receptors in atrial preparations but not in right or left ventricular preparations. Furthermore, the existence of a local myocardial angiotensin converting enzyme with functional importance is shown.