Role of endothelium in the modulation of isoflurane-induced vasodilatation in rat thoracic aorta.
The mechanisms by which endothelium attenuates vasodilation caused by isoflurane are not well understood. We examined the role of endothelium-derived substances, nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), prostanoids and endothelins in the response to isoflurane in rat thoracic aorta. Increasing cumulative concentrations of isoflurane were administered to aortic rings suspended in Hepes solution and preconstricted with either phenylephrine 10(-6) mol litre-1 or KCl 40 mmol litre-1 (which inhibit EDHF). Rings were intact, denuded or incubated with an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNNA 5 x 10(-5) mol litre-1), an inhibitor of prostanoid synthesis (indomethacin 10(-5) mol litre-1) or a blocker of the vascular receptors to endothelins (cyclo (-D-trp-D-Asp-Pro-D-Val-Leu (BQ 123 10(-5) mol litre-1)- Endothelium attenuated isoflurane-induced vasodilation in KCl-constricted rings at concentrations of 4% (mean 95 (SEM 4)% vs 72 (4)%; P = 0.0005) and 5% (100 (4)% vs 80 (4)%; P = 0.0008) and in phenylephrine constricted rings at concentrations of 4% (54 (8)% vs 35 (3)%; P = 0.04) and 5% (78 (10)% vs 49 (5)%; P = 0.03). Relaxation was significantly greater in rings treated with LNNA than in intact rings at concentrations of 4% (85 (4)% vs 72 (4)%; P = 0.0005) and 5% (90 (4)% vs 80 (4)%; P = 0.0008). Indomethacin and BQ 123 did not alter isoflurane-induced vasodilation. We conclude that endothelium attenuated the vasodilator effect of isoflurane by a mechanism which was abolished by inhibition of nitric oxide. We hypothesize that isoflurane inhibits the release of nitric oxide, leading to a relative vasoconstriction counter-balancing its vasodilator effect. In contrast, EDHF, prostanoids and endothelins were not involved in the attenuation of isoflurane-induced vasodilatation.
Kirstetter
P
P
Department of Anaesthesia, Hôpital Beaujon, Clichy, France.
Lagneau
F
F
Lucas
O
O
Krupa
Y
Y
Marty
J
J
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D007530:Isoflurane; D019001:Nitric Oxide Synthase