EFFECTS OF HALOTHANE, ENFLURANE AND ISOFLURANE ON CONTRACTION OF RAT AORTA INDUCED BY ENDOTHELIN-1

Volatile anaesthetics induce hypotension by both indirect and direct e ffects; they have been reported to inhibit vasoconstriction produced b y a variety of agonists. These studies were performed to see if haloth ane, enflurane and isoflurane attenuate endothelin-1-evoked contractio n and if they interact with endothelium-dependent or -independent vaso active substances. Rat aortic rings were suspended in aerated Krebs' s olution (37 degrees C) and contracted by incremental doses of endothel in-1 5x10(-10) to 5x10(-8) mol litre(-1). Volatile anaesthetics at 1 a nd 2 MAC were tested on endothelium intact and denuded rings. They wer e tested also on L-NAME incubated endothelium intact and indomethacin- incubated endothelium intact and denuded rings. Responses to endotheli n-1 were compared in the presence and absence of volatile anaesthetics . Isoflurane at I and 2 MAC con centration, and enflurane at 2 MAC, in duced a rightward shift of the dose-response curve obtained with endot helin-l in both endothelium denuded and intact rings, associated with a decrease in maximal tension generated in the latter rings. In L-NAME -incubated endothelium intact rings and in indomethacin endothelium de nuded rings, the anaesthetics induced a rightward shift of the dose-re sponse curve without modification of maximal tension. In indomethacin- incubated endothelium intact rings there was significant attenuation o f endothelin-l contraction in control rings which was not enhanced by volatile anaesthetics in treated rings. The present study indicates th at isoflurane at 1 and 2 MAC, and enflurane at 2 MAC, significantly de creased endothelin-l-induced contraction of isolated rat aorta. This i nhibition was observed in both intact and denuded rings and probably i nvolves mechanisms within the smooth muscle. Nevertheless, our results suggest that part of the anaesthetic-induced inhibition of endothelin -1-evoked vasocontraction involves an ''indomethacin-like'' effect on an endothelial-derived vasoconstricting cyclo-oxygenase product.