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Propofol inhibits phorbol 12, 13‐dibutyrate‐induced, protein kinase C‐mediated contraction of rat aortic smooth muscle
Author(s) -
Yu J.,
Kakutani T.,
Mizumoto K.,
Hasegawa A.,
Hatano Y.
Publication year - 2006
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2006.01119.x
Subject(s) - bisindolylmaleimide , protein kinase c , phorbol , contraction (grammar) , medicine , endocrinology , vascular smooth muscle , muscle contraction , vasodilation , phosphorylation , vasoconstriction , propofol , pharmacology , biology , smooth muscle , biochemistry
Background: Propofol induces dose‐dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)‐mediated Ca 2+ sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13‐dibutyrate; PDBu)‐induced, PKC‐mediated contraction of rat aortic smooth muscle. Methods: The PDBu‐induced contraction of endothelium‐denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu‐induced PKC phosphorylation of endothelium‐denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting. Results: PDBu, but not the inactive phorbol ester, 4‐α‐phorbol 12‐myristate‐13‐acetate, dose‐dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10 −6 M. The PDBu (10 −6 M)‐induced contraction was dose‐dependently inhibited by bisindolylmaleimide I with reductions of 6.8 ± 1.8% ( P > 0.05), 39.8 ± 8.7% ( P < 0.01) and 96.7 ± 1.4% ( P < 0.01) in response to concentrations of 5 × 10 −7 M, 10 −6 × M and 5 × 10 −6 M, respectively, and by propofol with decreases of 5.2 ± 1. 6% ( P > 0.05), 9.4 ± 1.7% ( P < 0.05), 65.3 ± 9.2% ( P < 0.01) and 96.2 ± 1.6% ( P < 0.01) in response to concentrations of 5 × 10 −7 M, 10 −6 M, 5 × 10 −6 M and 10 −5 M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu‐induced increase in the density of the phosphorylated PKC bands in a dose‐dependent manner, with decreases of 6.3 ± 2.8% ( P > 0.05), 42.9 ± 3.2% ( P < 0.01) and 96.6 ± 3.4% ( P < 0.01) in response to 5 × 10 −7 M, 10 −6 M or 5 × 10 −6 M bisindolylmaleimide I, respectively, and with decreases of 4.2 ± 2.5% ( P > 0.05), 13.5 ± 1.7% ( P < 0.05), 69.5 ± 3.5% ( P < 0.01) and 95.3 ± 4.3% ( P < 0.01) in response to 5 × 10 −7 M, 10 −6 M, 5 × 10 −6 M and 10 −5 M propofol, respectively. Conclusion: Propofol dose‐dependently inhibits PDBu‐induced, PKC‐mediated contraction of rat aortic smooth muscle.