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ANESTHETIC PHARMACOLOGY

The Mechanism Behind the Inhibitory Effect of Isoflurane on Angiotensin II-Induced Vascular Contraction Is Different from That of Sevoflurane

From the Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan.

Address correspondence and reprint requests to Koji Ogawa, MD, Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. Address e-mail to ogawak{at}wakayama-med.ac.jp.

BACKGROUND: Angiotensin II (Ang II)-induced vascular contraction is mediated both by a Ca²⁺-mediated signaling pathway and a Ca²⁺ sensitization mechanism. We recently demonstrated that sevoflurane inhibits the contractile response to Ang II, mainly by inhibiting protein kinase C (PKC) phosphorylation that regulates myofilament Ca²⁺ sensitivity, without significant alteration of intracellular Ca²⁺ concentration ([Ca²⁺]_i) in rat aortic smooth muscle. The current study was designed to determine the mechanisms by which isoflurane inhibits Ang II-induced contraction of rat aortic smooth muscle.

METHODS: The effects of isoflurane on vasoconstriction, increase in [Ca²⁺]_i, and phosphorylation of PKC in response to Ang II (10^–7 M) were investigated, using an isometric force transducer, a fluorometer, and Western blotting, respectively.

RESULTS: Ang II elicited a transient contraction of rat aortic smooth muscle that was associated with an increase in [Ca²⁺]_i and PKC phosphorylation. Isoflurane (1.2%–3.5%) inhibited Ang II-induced contraction of rat aortic smooth muscle in a concentration-dependent manner (P < 0.05 at 1.2%, P < 0.01 at 2.3% and 3.5% isoflurane, n = 6). Isoflurane also inhibited elevation of [Ca²⁺]_i in response to Ang II (P < 0.01 at 2.3% and 3.5% isoflurane, n = 6), but failed to affect Ang II-induced phosphorylation of PKC at concentrations up to 3.5% (n = 7).

CONCLUSION: These results suggest that, unlike sevoflurane, the inhibitory effect of isoflurane on Ang II-induced contraction is mainly mediated by attenuation of the Ca²⁺-mediated signaling pathway.

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