Nitric oxide synthase inhibition reduces wakefulness.
The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthase and L-arginine, a precursor of NO, was examined on the sleep-waking pattern in rats. L-NMMA (3.75-15 mg/kg, i.p.) reduced wakefulness with a corresponding increase of slow wave sleep and rapid eye movement sleep. The effect of L-NMMA on vigilance was limited to the first hour following drug administration. The effect of L-NMMA was abolished by intracerebroventricular administration of L-arginine (600 micrograms). This indicates that the inhibitory effect of L-NMMA on wakefulness is mediated by decreased NO synthesis and that central NO exerts an excitatory role in vigilance. It further implicates that factors facilitating a release and/or synthesis of NO might lead to increased wakefulness and sleep disturbances.
Dzoljic
M R
MR
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
De Vries
R
R
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001143:Arousal / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases