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.