Department of Anesthesia, Japan Red Cross Society Wakayama Medical Center, Wakayama, Japan.
J Anesth. 2010 Dec;24(6):893-900. doi: 10.1007/s00540-010-1033-z. Epub 2010 Oct 17.
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(2+)) and myofilament Ca(2+) 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(2+)-mediated pathways and Ca(2+) sensitization pathways of rat aortic smooth muscle.
The effects of isoflurane and sevoflurane on AVP-induced vasoconstriction and on the AVP-induced increase in Ca(2+) and Rho activity in rat aorta were investigated by isometric force recording, by measuring Ca(2+) using fluorescence dye, and by Western blotting techniques.
Arginine vasopressin (10⁻⁷M) elicited a transient contractile response that was inhibited by isoflurane and sevoflurane in a concentration-dependent manner. AVP (10⁻⁷ M) induced a transient increase in intracellular Ca(2+) concentration (Ca(2+)). Isoflurane and sevoflurane also inhibited an AVP-induced increase in Ca(2+) in a concentration-dependent manner. AVP (10⁻⁷ 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.
Arginine vasopressin-induced vasoconstriction is mediated by an increase in Ca(2+) 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.
精氨酸加压素（AVP）是一种强效的血管收缩剂，有时用于治疗难治性血管扩张性休克。AVP 通过增加细胞内钙离子浓度(Ca(2+))和肌球蛋白钙敏感性来收缩血管平滑肌。然而，挥发性麻醉剂对 AVP 介导的血管收缩的调节作用仍有待确定。本研究探讨了异氟烷和七氟烷对 AVP 诱导的血管收缩的影响，并阐明了潜在的机制，重点关注大鼠主动脉平滑肌中的 Ca(2+)介导途径和 Ca(2+)敏化途径。
通过等长力记录、荧光染料测量Ca(2+)和 Western blot 技术，研究了异氟烷和七氟烷对 AVP 诱导的血管收缩以及 AVP 诱导的大鼠主动脉Ca(2+)增加和 Rho 活性的影响。
AVP（10⁻⁷M）引发短暂的收缩反应，该反应可被异氟烷和七氟烷浓度依赖性抑制。AVP（10⁻⁷M）诱导细胞内钙离子浓度(Ca(2+))短暂增加。异氟烷和七氟烷也以浓度依赖性方式抑制 AVP 诱导的Ca(2+)增加。AVP（10⁻⁷M）增加 Rho 活性，2 个最低肺泡浓度的七氟烷（P < 0.01）减弱该活性，但等效力浓度的异氟烷则无此作用。
AVP 诱导的血管收缩是通过大鼠主动脉平滑肌中Ca(2+)的增加和 Rho-Rho 激酶途径的激活来介导的。虽然在临床相关浓度下，异氟烷和七氟烷均能减弱 AVP 诱导的收缩，但它们抑制作用的细胞机制似乎不同。
