Effects of inhibiting protein kinase C on Ca[sup]2+[/sup]-sensitivityof contractile machinery in vascular smooth muscle under vasospasm of different genesis
A.A. Pavlova, V.F. Sagach, A.I. Soloviev
Institute of Pharmacology and Toxicology Academy ofMedical Sciences of Ukraine, Kiev;А.А. Bogomoletz Institute of Physiology NationalAcademy of Sciences of Ukraine, Kiev
Abstract
The aim of the study was to investigate the role of protein
kinase C (PKC) in changes in myofilament Ca 2+-sensitivity
of vascular smooth muscle cells (SMC) in rats at different
vasospastic states: hypoxic pulmonary vasoconstriction, genetically
determined hypertension, and hypertension resulted from ionizing radiation. All vasospastic states demonstrated
rightward shifts in pCa-tension curves suggesting that myofilament
Ca 2+-sensitivity had increased. In chemically (?-es-
cin) skinned pulmonary artery, hypoxia-induced increase in
myofilament Ca2+-sensitivity was completely abolished by
PKC inhibitor chelerythrine. The similar results were demon-
strated in skinned aorta SMC of spontaneously hypertensive
rats where an increase in myofilament Ca2+-sensitivity was
also abolished by PKC inhibitors chelerythrine and stauro-
sporine. The chelerythrine partially inhibited myofilament
Ca2+-sensitivity that had increased following ?-radiation. The
data suggest the key role of PKC activity in modulation of
myofilament Ca 2+-sensitivity in SMC. We conclude that PKC-
mediated increase in myofilament Ca 2+-sensitivity is one of
the main mechanisms which contribute to the vasospasm of
different genesis.
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