Isoflurane inhibits endothelium-mediated nitric oxide relaxing pathways in the isolated perfused rabbit lung.
OBJECTIVE
The role of volatile anaesthetics on nitric oxide (NO)-dependent relaxation is unclear in the pulmonary circulation. We examined the effects of isoflurane on NO-dependent relaxation in isolated perfused rabbit lungs.


METHODS
Eighteen rabbit lungs were perfused in a constant-flow recirculation manner. In study 1 (n = 12), acetylcholine (ACh, 4 x 10(-10)-10(-8) M) or nitroglycerine (NTG, 6 x 10(-10)-10(-8) M) was cumulatively injected into the pulmonary artery in the absence or presence of isoflurane (1, 2 MAC). In study 2 (n = 6), ACh was injected as in study 1 in the presence or absence of N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), an NO synthesis blocker. In all experiments, indomethacin was administered to prevent formation of vasoactive prostanoid metabolites, and the pulmonary vessels were preconstricted with prostaglandin F2 alpha (PGF2 alpha) infused before ACh or NTG injection. The ACh- or NTG-induced relaxation was expressed as % decrease in PGF2 alpha preconstriction.


RESULTS
Isoflurane at 2 MAC attenuated the dose-dependent relaxation to ACh at doses of 4 x 10(-9) M and 4 x 10(-8) M from 27.8 +/- 4.3% and 38.8 +/- 5.3% to 17.0 +/- 3.5% and 25.5 +/- 4.9%, respectively (P < 0.05). Isoflurane did not change the dose-dependent relaxation to NTG and L-NAME abolished the ACh-induced relaxation.


CONCLUSIONS
Isoflurane inhibited NO-dependent relaxation in the pulmonary circulation at a site distal to the endothelial cell receptor-mediated responses but proximal to guanylate cyclase activation of vascular smooth muscle. Acetylcholine-induced relaxation in isolated perfused rabbit lungs was regulated primarily by NO.
Oshima
Y
Y
Department of Anesthesiology, Faculty of Medicine, Tottori University, Yonago, Japan. yoshimat@grape.med.tottori-u.ac.jp
Ishibe
Y
Y
Okazaki
N
N
Sato
T
T
D000109:Acetylcholine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester