The cellular mechanisms underlying the inhibitory effects of isoflurane and sevoflurane on arginine vasopressin-induced vasoconstriction.
OBJECTIVE
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+)](i)) 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.


METHODS
The effects of isoflurane and sevoflurane on AVP-induced vasoconstriction and on the AVP-induced increase in [Ca(2+)](i) and Rho activity in rat aorta were investigated by isometric force recording, by measuring [Ca(2+)](i) using fluorescence dye, and by Western blotting techniques.


RESULTS
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+)](i)). Isoflurane and sevoflurane also inhibited an AVP-induced increase in [Ca(2+)](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.


CONCLUSIONS
Arginine vasopressin-induced vasoconstriction is mediated by an increase in [Ca(2+)](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.
Department of Anesthesia, Japan Red Cross Society Wakayama Medical Center, Wakayama, Japan.
Manabu
M
Shimogai
Koji
K
Ogawa
Yasuyuki
Y
Tokinaga
Akinori
A
Yamazaki
Yoshio
Y
Hatano
D008841:Actin Cytoskeleton / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000077149:Sevoflurane; D007530:Isoflurane; D054460:rho-Associated Kinases; D002118:Calcium