Nitric oxide synthase inhibition reduces wakefulness

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The effect of N G - 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 μg). 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.