Selective impairment of endothelium-dependent relaxation by sevoflurane: oxygen free radicals participation.
To determine whether sevoflurane alters endothelium-mediated vasodilation of vascular smooth muscle, isolated ring preparations of canine mesenteric arteries were suspended for isometric tension recordings in modified Krebs-Ringer bicarbonate solution at 37 degrees C. Following contraction with norepinephrine, cumulative concentration-response curves were generated using endothelium-dependent vasodilators (acetylcholine, bradykinin, and calcium ionophore A23187) or nitroglycerin. The relaxation produced by acetylcholine, bradykinin, or A23187 was impaired by sevoflurane (2.3 and 4.6 vol%); sevoflurane did not affect relaxation caused by nitroglycerin, which, in these vessels, acts by an endothelium-independent mechanism. Under the same experimental conditions as those used for the concentration-response relationship, electron spin resonance spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide verified generation of hydroxyl radical from the sevoflurane-delivered bathing media; the generation of hydroxyl radical was inhibited by superoxide dismutase, a scavenger of superoxide anion radical, or by the powerful iron chelator deferoxamine. Furthermore, sevoflurane-induced impairment of the relaxation caused by the endothelium-dependent vasodilators used was significantly decreased by superoxide dismutase. These results indicate that superoxide anion radical and/or closely related species of oxygen free radicals, possibly hydroxyl radical, are involved in the observed effect of sevoflurane. We propose that sevoflurane selectively impairs endothelium-dependent relaxation in canine mesenteric arteries by an oxygen free radical mechanism, mainly due to inactivation of endothelium-derived relaxing factor.
Yoshida
K
K
Department of Anesthesiology, Kanagawa Dental College, Japan.
Okabe
E
E
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004987:Ethers / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D008738:Methyl Ethers; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000502:physiology*; D000077149:Sevoflurane; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000777:Anesthetics; D004987:Ethers; D005609:Free Radicals; D008738:Methyl Ethers; D000077149:Sevoflurane; D010100:Oxygen