Effects of halothane, enflurane and isoflurane on contraction of rat aorta induced by endothelin-1.
Volatile anaesthetics induce hypotension by both indirect and direct effects; they have been reported to inhibit vasoconstriction produced by a variety of agonists. These studies were performed to see if halothane, enflurane and isoflurane attenuate endothelin-1-evoked contraction and if they interact with endothelium-dependent or -independent vasoactive substances. Rat aortic rings were suspended in aerated Krebs' solution (37 degrees C) and contracted by incremental doses of endothelin-1 5 x 10(-10) to 5 x 10(-8) mol litre-1. Volatile anaesthetics at 1 and 2 MAC were tested on endothelium intact and denuded rings. They were tested also on L-NAME incubated endothelium intact and indomethacin-incubated endothelium intact and denuded rings. Responses to endothelin-1 were compared in the presence and absence of volatile anaesthetics. Isoflurane at 1 and 2 MAC concentration, and enflurane at 2 MAC, induced a rightward shift of the dose-response curve obtained with endothelin-1 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 denuded rings, the anaesthetics induced a rightward shift of the dose-response curve without modification of maximal tension. In indomethacin-incubated endothelium intact rings there was significant attenuation of endothelin-1 contraction in control rings which was not enhanced by volatile anaesthetics in treated rings. The present study indicates that isoflurane at 1 and 2 MAC, and enflurane at 2 MAC, significantly decreased endothelin-1-induced contraction of isolated rat aorta. This inhibition was observed in both intact and denuded rings and probably involves 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.
Boillot
A
A
Department of Anesthesiology, Centre Hospitalier Régional Universitaire, Besançon, France.
Vallet
B
B
Marty
J
J
Auclerc
A
A
Barale
F
F
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D016232:Endothelins; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane