Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated contraction of rat aortic smooth muscle

Abstract

Background: Propofol induces dose-dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)-mediated Ca2+ 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. © 2006 The Authors.