Key result
The PKC inhibitor staurosporine (80 nM) significantly decreased stiffness but had little effect on stress, MLC phosphorylation, or shortening velocity in ET-1-stimulated swine carotid media.
Inhibition of PKC activity with staurosporine alters the stress-stiffness relationship during ET-1-induced contractions in swine carotid media, suggesting a change in cross-bridge mechanics.
Hypothesis-generating for PKC modulation of arterial stiffness; requires in vivo confirmation before clinical consideration.
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.
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Moreland et al. (1992) studied this question. Staurosporine was evaluated on Stiffness, stress, MLC phosphorylation, and shortening velocity. The PKC inhibitor staurosporine (80 nM) significantly decreased stiffness but had little effect on stress, MLC phosphorylation, or shortening velocity in ET-1-stimulated swine carotid media.
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