The effects of the nitric oxide synthase inhibitor 7-nitroindazole on ethanol pharmacokinetics in rats after acute and chronic ethanol administration

The aim of this work was to study the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI) and NO-nitro-L-arginine (L-NOARG) o n the effects and pharmacokinetics of ethanol in rats. Ethanol at a dose of 3 g/kg, i.p, induced sleep in rats (sleep time: 117.2 +/- 30.7 min). Admin istration of the NOS inhibitors 7-NI (20 mg/kg, i.p.) and L-NOARG (20 mg/kg , i.p.) 30 min before ethanol significantly increased the duration of ethan ol-induced sleep. L-NOARG also significantly increased the toxicity of etha nol as evidenced by increased post-experimental lethality. Ethanol at a dos e of 2 g/kg (i.p.) did not induce sleep in vehicle-treated rats; however, t he combined administration of ethanol (2 g/kg) and 7-NI at doses of 40, 80, and 120 mg/kg caused sleep, for 49.4 +/- 3.7, 204.0 +/- 13.3, and 447.5 +/ - 62.8 min, respectively. L-NOARG (20 mg/kg;) had no effect on ethanol conc entrations in blood after acute ethanol administration (4 g/kg). 7-NI in lo wer doses (20 and 40 mg/kg) had no effect and in higher doses (80 and 120 m g/kg) significantly slowed ethanol clearance during the 12 h after ethanol administration. The effect of 7-NI (20 mg/kg) on ethanol pharmacokinetics a fter chronic ethanol administration (inhalation for 18 days) was also studi ed. The administration of 7-NI immediately after the end of ethanol exposur e had a pronounced effect on ethanol pharmacokinetics; in 7-NI-treated rats the fall in ethanol concentrations was significantly slower as compared wi th vehicle-treated rats. In 7-NI-treated rats, blood-ethanol levels were hi gher at 3, 6, 9, and 12 h after the end of ethanol exposure.