AJP - Cell Physiology, Vol 262, Issue 4 C862-C869, Copyright © 1992 by American Physiological Society
Staurosporine decreases stiffness but not stress in endothelin-1-stimulated arterial muscle
R. S. Moreland, J. Cilea and S. Moreland
Bockus Research Institute, Graduate Hospital, Philadelphia, Pennsylvania 19146.
Endothelin-1 (ET-1) is one of the most potent naturally occurring
vasoconstrictors. The mechanism(s) by which ET-1 contracts vascular smooth
muscle remains controversial. This study was designed to determine the
effects of ET-1 on stress, stiffness, shortening velocity, and myosin light
chain (MLC) phosphorylation in swine carotid media. The source of activator
Ca2+ for the contractions and the role of protein kinase C (PKC) were
determined. The results demonstrate that ET-1 contractions of the swine
carotid media are supported primarily by the influx of extracellular Ca2+.
The ET-1-stimulated contraction is characterized by rapid, transient
increases in MLC phosphorylation levels and shortening velocity, whereas
stiffness and stress increase monotonically. The PKC inhibitor
staurosporine (80 nM) significantly decreased stiffness but had little
effect on stress, MLC phosphorylation, or shortening velocity. Thus
inhibition of PKC activity alters the stress-stiffness relationship during
ET-1-induced contractions. This alteration could result from a change in
the stress generated per cross bridge or by a cooperative mechanism for
cross-bridge attachment that does not affect stress development.
