Inhibitory effect of sevoflurane on nitric oxide release from cultured endothelial cells.
We investigated the effect of sevoflurane (fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl) ethylether) on intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) release from cultured porcine aortic endothelial cells using fura-2 fluorometry, and direct (ESR spectrometry with NO-trapping by 2-(4-carboxyphenyl)-4,4,5,5-tetramiethylimidazoline-1-oxyl 3-oxide) or indirect (nitrite accumulation measured by Greiss reaction) NO measurement. Sevoflurane alone did not change resting [Ca2+]i, but diminished bradykinin-induced transient increase in [Ca2+]i in a concentration-dependent manner. The inhibitory effect of sevoflurane on bradykinin-induced transient rise in [Ca2+]i was larger than that of a non-selective Ca2+ channel blocker (CO2+). Application of sevoflurane following bradykinin-evoked [Ca2+]i transient diminished [Ca2+]i significantly, while bradykinin B2 receptor antagonist (D-Arg-[Hyp3, Thi5,8, D-Phe7] bradykinin) or CO2+ abolished it. Sevoflurane impaired nitrite accumulation stimulated by bradykinin, and reduced the amount of NO released from endothelial cells. Our results indicate that the negative effect of sevoflurane appears to be due to the inhibition of bradykinin-induced Ca2+ efflux from endoplasmic stores and Ca2+ influx through membrane Ca2+ channels.
Az-ma
T
T
Department of Anesthesiology and Critical Care Medicine, Hiroshima University, School of Medicine, Japan.
Fujii
K
K
Yuge
O
O
D000704:Analysis of Variance; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology*; D008738:Methyl Ethers; D009569:Nitric Oxide / Q000378:metabolism*; D000077149:Sevoflurane; D013552:Swine
D000777:Anesthetics; D004987:Ethers; D008738:Methyl Ethers; D009569:Nitric Oxide; D000077149:Sevoflurane; D002118:Calcium