The cellular mechanisms underlying the inhibitory effects of isoflurane and sevoflurane on arginine vasopressin-induced vasoconstriction

Shimogai, Manabu; Ogawa, Koji; Tokinaga, Yasuyuki; Yamazaki, Akinori; Hatano, Yoshio
December 2010
Journal of Anesthesia;2010, Vol. 24 Issue 6, p893
Academic Journal
Purpose: Arginine vasopressin (AVP) is a potent vasoconstrictor that is sometimes used for the treatment of refractory vasodilatory shock. AVP constricts vascular smooth muscle by increasing both intracellular calcium concentration ([Ca]) and myofilament Ca sensitivity. However, the modulation of AVP-mediated vasoconstriction by volatile anesthetics remains to be determined. This study investigates the effects of isoflurane and sevoflurane on AVP-induced vasoconstriction and elucidates the underlying mechanisms, with an emphasis on the Ca-mediated pathways and Ca sensitization pathways of rat aortic smooth muscle. Methods: The effects of isoflurane and sevoflurane on AVP-induced vasoconstriction and on the AVP-induced increase in [Ca] and Rho activity in rat aorta were investigated by isometric force recording, by measuring [Ca] using fluorescence dye, and by Western blotting techniques. Results: Arginine vasopressin (10M) elicited a transient contractile response that was inhibited by isoflurane and sevoflurane in a concentration-dependent manner. AVP (10 M) induced a transient increase in intracellular Ca concentration ([Ca]). Isoflurane and sevoflurane also inhibited an AVP-induced increase in [Ca] in a concentration-dependent manner. AVP (10 M) increased the Rho activity that was attenuated by 2 minimum alveolar concentration of sevoflurane ( P < 0.01), but not by an equipotent concentration of isoflurane. Conclusion: Arginine vasopressin-induced vasoconstriction is mediated by an increase in [Ca] and by the activation of the Rho-Rho kinase pathway in rat aortic smooth muscle. Although both isoflurane and sevoflurane, at clinically relevant concentrations, attenuate AVP-induced contraction, the cellular mechanisms of their inhibitory effects appear to differ.


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