AJP - Heart and Circulatory Physiology, Vol 253, Issue 2 444-H453, Copyright © 1987 by American Physiological Society
Myocardial adaptation to chronic propranolol therapy in normal rats
F. S. Fein, B. Zola, B. Miller, A. Malhotra and E. H. Sonnenblick
The intrinsic myocardial adaptation to chronic beta-blockade was explored
in normal male Wistar rats. Propranolol was administered by subcutaneous
infusion using osmotic minipumps for 3-4 wk (P group). Heart rate fell by
approximately 100 beats/min. A second group of animals was similarly
treated but had their pumps removed several days before study (P-R group).
Heart rate rose, but remained below base line. Study of isolated
ventricular papillary muscle from P, P-R, and age-matched controls (C
group) revealed prolonged contraction duration in P and P-R groups, but no
change in shortening velocity. A greater shortening of time to peak tension
and time to one-half relaxation in response to norepinephrine was
demonstrated in P and P-R groups. Acute in vivo or in vitro administration
of propranolol had no effect on base-line mechanical performance. No
changes in the Ca2+, actin-activated Mg2+ myosin adenosine triphosphatase
(ATPase) activity, or myosin isoenzyme distribution were found. Free
thyroxine levels were decreased in P but not P-R groups. These findings
indicate that chronic propranolol therapy in normal rats slows contraction
and relaxation without altering contractility. The greater shortening of
contraction duration in response to norepinephrine is partly offset by the
prolongation of the base-line contraction.
