EFFECT OF SEVOFLURANE ON THE VASCULAR REACTIVITY OF RABBIT MESENTERIC-ARTERY

Sevoflurane is well known to cause depression of cardiovascular functi on, but detailed information on its actions on the contractility and r eactivity of blood vessels is lacking. We have assessed therefore the direct effect of th is anaesthetic on the functional reactivity of iso lated rabbit mesenteric artery ring preparations. We found that contra ctions of endothelium intact rings induced by noradrenaline and phenyl ephrine were significantly attenuated by 4% sevoflurane; the observati on that the maximal tension generation decreased without a significant reduction in pD(2) is consistent with the view that receptor dysfunct ion was not involved. The effect of sevoflurane was not affected by N- G-monomethyl-L-arginine. Sevoflurane 4% also produced attenuation of n oradrenaline-induced contractions of endothelium denuded ring preparat ions. The contractions of endothelium denuded ring preparations produc ed by noradrenaline in Ca2+-free media in the presence of K+ were not affected by 4% sevoflurane, but sevoflurane depressed external Ca2+-de pendent contractions. When vasodilators (acetylcholine and nitroglycer in) were added to the bathing media in the presence of 2% sevoflurane, the endothelium-dependent relaxation produced by acetylcholine, but n ot the endothelium-independent relaxation produced by nitroglycerin, w as attenuated; superoxide dismutase inhibited the effect of sevofluran e on endothelium-dependent relaxation. These results are consistent wi th the view that sevoflurane inhibits alpha adrenoceptor-mediated cont ractions of isolated rabbit mesenteric artery ring preparations; this effect may be caused by reduced Ca2+ influx, as estimated from the eff ect on external Ca2+-dependent contractions, but is unlikely to be cau sed by reduced Ca2+ release from the sarcoplasmic reticulum of vascula r smooth muscle, as estimated from noradrenaline-induced contractions in Ca2+-free bathing media. Sevoflurane may selectively attenuate endo thelium-dependent relaxation by an oxygen free radical mechanism as op posed to endothelium-independent relaxation.