Circulation, Vol 82, 1973-1984, Copyright © 1990 by American Heart Association
CS Moravec, MD Schluchter, L Paranandi, B Czerska, RW Stewart, E Rosenkranz and M Bond
The direct effects of angiotensin II (Ang II) on human cardiac muscle were
investigated using isolated trabecular muscles from failing and
functionally normal hearts. Atrial and ventricular trabeculae were studied.
Results demonstrated a positive inotropic effect of Ang II on human cardiac
muscle. Comparison of the effects of Ang II among groups indicated that the
responsiveness tended to be greater in atrial and normal muscle compared
with failing muscle. Results of this study also demonstrated heterogeneity
in the responsiveness to Ang II among human muscles, which was not
correlated with patient age, sex, diagnosis, prior treatment with
angiotensin converting enzyme inhibitor, or heart function. A significant
correlation between response to Ang II and response to isoproterenol was
demonstrated in failing ventricular trabeculae, which may suggest that
defects in beta-adrenergic responsiveness in the failing human ventricle
are accompanied by a loss of responsiveness to Ang II. Studies were
extended to the Syrian cardiomyopathic hamster and its control. A
dose-dependent inotropic response occurred in normal hamster ventricular
muscle but was significantly diminished in cardiomyopathic muscle. Ang II
did not shorten the timing of contraction, and pretreatment with
adrenergic- blocking agents did not shift the dose-response curve,
indicating that the response was not cyclic AMP mediated. This study
demonstrates for the first time that Ang II can exert an inotropic effect
directly on human cardiac muscle and confirms that there is a direct effect
of Ang II on hamster cardiac muscle. The study further suggests, however,
that the inotropic response to Ang II in cardiac muscle is heterogeneous
and may be diminished by heart failure.
ARTICLES
Inotropic effects of angiotensin II on human cardiac muscle in vitro
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio 44195-5069.
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