Circulation, Vol 88, 1228-1237, Copyright © 1993 by American Heart Association
C Holubarsch, G Hasenfuss, S Schmidt-Schweda, A Knorr, B Pieske, T Ruf, R Fasol and H Just
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.
ARTICLES
Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. An in vitro study under physiological experimental conditions
Department of Cardiology, Internal Medicine, University of Freiburg, Germany.
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