Circulation, Vol 89, 2492-2497, Copyright © 1994 by American Heart Association
AM Shah, A Mebazaa, RC Wetzel and EG Lakatta
BACKGROUND: Recent studies suggest that both endocardial endothelium and
coronary vascular endothelium influence myocardial contraction, but the
mediators responsible and their mechanisms of action are not well defined.
METHODS AND RESULTS: We investigated the effects of cultured endocardial
endothelial and vascular endothelial cell superfusate on contraction and
intracellular calcium transients of isolated rat cardiac myocytes.
Endothelial cell superfusate induced a potent negative inotropic effect,
with a rapid reversible decrease in myocyte twitch amplitude, earlier
twitch relaxation, and a significant increase in diastolic length. This
effect was not associated with significant changes in intracellular calcium
or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein
kinase C activation; and did not involve pertussis toxin-sensitive G
proteins. The activity was stable at 37 degrees C for several hours, was
not destroyed by protease treatment, and was found in low-molecular-weight
(<< 1 kD) superfusate fractions. CONCLUSIONS: These data suggest the
tonic release by endothelial cells of a novel, stable factor that acts
predominantly by reducing the response of cardiac myofilaments to calcium
(ie, "desensitizes" them). This "desensitizing factor" could rapidly
modulate cardiac contraction-relaxation coupling and diastolic tonus and
exert distant effects because of its stability.
ARTICLES
Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
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