Sevoflurane Inbibits Angiotensin II-induced, Protein Kinase C-mediated but Not Ca2+-elicited Contraction of Rat Aortic Smooth Muscle

Abstract

Background: Whether volatile anesthetics attenuate angiotensin II-mediated vascular tone has not been determined. The current study was designed to investigate the effects of sevoflurane on the angiotensin II-stimulated, Ca 2+- and protein kinase C (PKC)-mediated contraction of rat aortic smooth muscle. Methods: The dose-dependent effects of sevoflurane on angiotensin II (10-7 M)-induced contraction, the increase in intracellular Ca2+ concentration, and PKC phosphorylation of rat aortic smooth muscle were measured using an isometric force transducer, a fluorometer, and Western blotting, respectively. Results: Angiotensin II induced a transient increase in intracellular Ca2+ concentration, phosphorylation of Ca2+-dependent PKC (cPKC)-α, and consequently, a transient contraction of rat aortic smooth muscle. Phosphorylation of the Ca2+independent PKC-ε was not detected. The angiotensin II-induced contraction was almost completely abolished by removing extracellular Ca2+ and was significantly inhibited by the selective cPKC inhibitor Gö 6976 (10-5 M) but was not inhibited by the nonselective PKC inhibitor Ro 31-8425 (10-5 M). Sevoflurane dose-dependently inhibited the angiotensin II-induced contraction, with reductions of 14.2 ± 5.2% (P > 0.05), 26.7 ± 8.9% (P < 0.05), and 38.5 ± 12.8% (P < 0.01) (n = 10) in response to 1.7, 3.4, and 5.1% sevoflurane, respectively. The angiotensin II-elicited increase in intracellular Ca2+ concentration was not significantly influenced by 3.4, 5.1, or 8.5% sevoflurane. However, cPKC-α phosphorylation induced by angiotensin II was inhibited dose dependently by 1.7, 3.4, and 5.1% sevoflurane, with depressions of 20.5 ± 14.2% (P > 0.05), 37.0 ± 17.8% (P < 0.05), and 62.5 ± 12.2% (P < 0.01) (n = 4), respectively. Conclusion: The current study indicates that Ca2+ and cPKC-α are involved in angiotensin II-induced vascular contraction. Sevoflurane dose-dependently inhibited the angiotensin II-stimulated, cPKC-mediated but not Ca2+-elicited contraction of rat aortic smooth muscle.