AJP - Heart and Circulatory Physiology, Vol 258, Issue 6 1727-H1734, Copyright © 1990 by American Physiological Society
Normal responsiveness to external Ca and to Ca-channel modifying agents in hypertrophied rat heart
F. Callens-el Amrani, E. Mayoux, C. Mouas, R. Clapier-Ventura, D. Henzel, D. Charlemagne and B. Swynghedauw
Institut National de la Sante et de Recherche Medicale (INSERM) U127, Hopital, Paris, France.
In rat heart, the maximum velocity of shortening is decreased in response
to chronic pressure overload. This is in part explained by an isomyosin
shift, but several arguments suggest changes in membrane proteins.
Inotropic response to calcium channel modifiers and to external calcium
were simultaneously determined to explore this possibility. Left
ventricular hypertrophy was induced by abdominal aortic stenosis and after
4-5 wk the left ventricular-to-body weight ratio increased by 61%. The
effects of BAY K 8644 (10(-9) to 10(-6) M), a calcium channel activator,
nifedipine (10(-9) to 10(-7) M), and external calcium (0.25-2.50 mM) were
studied on isolated hearts at a coronary flow of 20 ml.min-1.g of left
ventricle-1. The inotropic response (in percent changes in developed
pressure and in dP/dtmax) was unmodified in the hypertrophied hearts. This
work is in agreement with previous findings that both the total number of
dihydropyridine binding sites and the peak magnitude of calcium current
increase in proportion to the degree of hypertrophy. It suggests that the
slowing of velocity could not be explained by a decreased number of Ca2+
channels but may more likely reflect modifications of the sarcomeres or
sarcoplasmic reticulum.
