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

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Abstract

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 ([Ca2+] i ) and myofilament Ca2+ 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 Ca2+-mediated pathways and Ca2+ 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 [Ca2+] i and Rho activity in rat aorta were investigated by isometric force recording, by measuring [Ca2+] i using fluorescence dye, and by Western blotting techniques.

Results

Arginine vasopressin (10−7 M) 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 Ca2+ concentration ([Ca2+] i ). Isoflurane and sevoflurane also inhibited an AVP-induced increase in [Ca2+] i 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.

Conclusion

Arginine vasopressin-induced vasoconstriction is mediated by an increase in [Ca2+] i 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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Acknowledgments

Financial support was provided solely from institutional and departmental sources.

Conflict of interest

None of the authors have any conflicts of interest.

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Authors and Affiliations

  1. Department of Anesthesia, Japan Red Cross Society Wakayama Medical Center, Wakayama, Japan

    Manabu Shimogai & Akinori Yamazaki

  2. Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan

    Koji Ogawa, Yasuyuki Tokinaga & Yoshio Hatano

Authors
  1. Manabu Shimogai
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  2. Koji Ogawa
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  3. Yasuyuki Tokinaga
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  4. Akinori Yamazaki
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  5. Yoshio Hatano
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Corresponding author

Correspondence to Koji Ogawa.

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Shimogai, M., Ogawa, K., Tokinaga, Y. et al. The cellular mechanisms underlying the inhibitory effects of isoflurane and sevoflurane on arginine vasopressin-induced vasoconstriction. J Anesth 24, 893–900 (2010). https://doi.org/10.1007/s00540-010-1033-z

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  • DOI: https://doi.org/10.1007/s00540-010-1033-z

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