Anaesthetic agents decrease the activity of nitric oxide synthase from human polymorphonuclear leucocytes.
Nitric oxide (NO) inhibitors reduce the threshold for anaesthesia. We have investigated the action of anaesthetic agents on human nitric oxide synthase (NOS) activity. Thiopentone reduced mean NOS activity to 36.6 (SD 8.9) % of control at 100 mumol litre-1 (P < 0.001) and 50.9 (20.3) % at 1 mmol litre-1 (P < 0.05). Ketamine showed similar effects, with activity reduced to 67.0 (17.6) % (P < 0.05) and 57.7 (8.5) % (P < 0.001) at 100 mumol litre-1 and 1 mmol litre-1, respectively. Etomidate 100 mumol litre-1 did not significantly alter activity (88.2 (8.1) %) but 1 mmol litre-1 did (60.6 (10.4) %, P < 0.005). Halothane also caused a significant decrease in NOS activity at all concentrations. This effect was specific as other enzymes were unaffected. We conclude that anaesthetic agents have a profound effect on NOS activity and as inhibition of NO release augments anaesthesia, we suggest that this may play a role in the mechanism of anaesthesia in humans.
Galley
H F
HF
Clinical Oxidant Research Group, St James's University Hospital, Leeds, UK.
Nelson
L R
LR
Webster
N R
NR
D000777:Anesthetics / Q000494:pharmacology*; D001120:Arginine / Q000097:blood; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors; D005045:Etomidate / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D013874:Thiopental / Q000494:pharmacology
D000777:Anesthetics; D002148:Calmodulin-Binding Proteins; D007649:Ketamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D013874:Thiopental; D006221:Halothane; D005045:Etomidate