Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+-dependent and PKC-mediated Ca2+ sensitization mechanisms

Angiotensin II (Ang II)-induced vascular contraction is mediated by Ca2+-dependent mechanisms and Ca2+ sensitization mechanisms. The phosphorylation of protein kinase C (PKC) regulates myofilament Ca2+ sensitivity. We have previously demonstrated that sevoflurane inhibits Ang II-induced vasoconstriction by inhibiting PKC phosphorylation, whereas isoflurane inhibits Ang II-induced vasoconstriction by decreasing intracellular Ca2+ concentration ([Ca2+](i)) in vascular smooth muscle. Propofol also induces vasodilation; however, the effect of propofol on PKC-mediated myofilament Ca2+ sensitivity is poorly understood. The aim of this study is to determine the mechanisms by which propofol inhibits Ang II-induced vascular contraction in rat aortic smooth muscle. An isometric force transducer was used to investigate the effect of propofol on vasoconstriction, a fluorometer was used to investigate the change in [Ca2+](i), and Western blot testing was used to analyze Ang II-induced PKC phosphorylation. Ang II (10(-7) M) elicited a transient contraction of rat aortic smooth muscle, which was associated with an elevation of [Ca2+](i). Propofol (10(-6) M) inhibited Ang II-induced vascular contraction (P < 0.01) and increase in [Ca2+](i) (P < 0.05) in rat aortic smooth muscle. Ang II also induced a rapid increase in [Ca2+](i) in cultured vascular smooth muscle cells, which was suppressed by propofol (P < 0.05). Propofol (10(-6) M) attenuated Ang II-stimulated PKC phosphorylation (P < 0.05). These results suggest that the inhibitory effect of propofol on Ang II-induced vascular contraction is mediated by the attenuation of a Ca2+-dependent pathway and Ca2+ sensitivity through the PKC signaling pathway.