Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting [Ca.sup.2+]-dependent and PKC-mediated [Ca.sup.2+] sensitization mechanisms

Purpose Angiotensin II (Ang II)-induced vascular contraction is mediated by [Ca.sup.2+]-dependent mechanisms and [Ca.sup.2+] sensitization mechanisms. The phosphorylation of protein kinase C (PKC) regulates myofilament [Ca.sup.2+] sensitivity. We have previously demonstrated that sevoflurane inhibits Ang II-induced vasoconstriction by inhibiting PKC phosphorylation, whereas isoflurane inhibits Ang IIinduced vasoconstriction by decreasing intracellular [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) in vascular smooth muscle. Propofol also induces vasodilation; however, the effect of propofol on PKC-mediated myofilament [Ca.sup.2+] 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. Methods An isometric force transducer was used to investigate the effect of propofol on vasoconstriction, a fluorometer was used to investigate the change in [[[Ca.sup.2+]].sub.i], and Western blot testing was used to analyze Ang II-induced PKC phosphorylation. Results Ang II ([10.sup.-7] M) elicited a transient contraction of rat aortic smooth muscle, which was associated with an elevation of [[[Ca.sup.2+]].sub.i]. Propofol ([10.sup.-6] M) inhibited Ang IIinduced vascular contraction (P < 0.01) and increase in [[[Ca.sup.2+]].sub.i] (P < 0.05) in rat aortic smooth muscle. Ang II also induced a rapid increase in [[[Ca.sup.2+]].sub.i] in cultured vascular smooth muscle cells, which was suppressed by propofol (P < 0.05). Propofol ([10.sup.-6] M) attenuated Ang II-stimulated PKC phosphorylation (P < 0.05). Conclusion These results suggest that the inhibitory effect of propofol on Ang II-induced vascular contraction is mediated by the attenuation of a [Ca.sup.2+]-dependent pathway and [Ca.sup.2+] sensitivity through the PKC signaling pathway. Keywords Artery * Calcium * Propofol * Protein kinase C