Mechanisms of inhibition of endothelium-dependent relaxation by halothane, isoflurane, and sevoflurane

Abstract

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitroprusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10(-7)-10(-5) M)-induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10(-8) M)-induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10(-7) M)-stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endothelium-dependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.

Sevoflurane reduces endothelium-dependent vasorelaxation: role of Superoxide anion and endothelin

“…[14][15][16] NO is degraded by free radicals, particularly by superoxide anion. We then determined the effect of sevoflurane on the ability of the vascular wall to release superoxide anion.…”

The Mechanisms of the Direct Vascular Effects of Sevoflurane on Saphenous Veins in Vitro

“…Nitric oxide is generated from the metabolic conversion of L-arginine into L-citrulline by the activity of the endothelial nitric oxide synthase. It relaxes vessels by stimulating guanylate cyclase in underlying smooth muscle cells (6). To assess the role of nitric oxide, we have compared the effect of sevoflurane between intact strips and strips incubated with L-NAME, a nitric oxide synthase inhibitor.…”

“…Akata et al, reported that anesthetic concentrations of sevoflurane have endothelium-independent inhibitory effects on vascular smooth muscle of isolated rabbit mesenteric artery (4). Other studies, sevoflurane decreases endotel dependent vascular relaxations to acetylcholine in rat mesenteric artery and aorta (5,6). However, in these studies differences in the mechanisms of vascular effect of sevoflurane had been shown.…”

The pressure fl ow relationship of the internal mammary artery after offpump anastomosis to the left anterior descending coronary artery

“…(17) Evidence also exists that sevofl urane decreases the sensitising of contractile proteins by calcium, however the exact mechanism is not fully understood. (18) In addition sevofl urane inhibits the second messenger IP3 which is responsible for calcium release intracellularly. (19) It does this to a lesser extent than either halothane or propofol.…”