Pressor effect of NG-nitro-L-arginine in pentobarbital-anesthetized rats

The pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, was studied in pentobarbital anesthetized rats. Iv injections of L-NNA from 0.25 to 8 mg/kg caused bradycardia and a dose-dependent increase in mean arterial pressure (MAP) with a maximal response of 43 +/- 5 mmHg and ED50 value of 1.3 +/- 0.2 mg/kg. The time course of the response to the injection of a single dose of L-NNA was also determined. Peak response was reached 60 min after the injection of a single dose (4 mg/kg, iv) and the effect lasted greater than 5 h. The rising phase of the pressor response was accompanied by slight bradycardia while the recovery phase was associated with significant tachycardia. Iv injections of L-arginine (12.5-200 mg/kg) caused transient dose-dependent reductions in MAP. The pressor effect of L-NNA (4 mg/kg, iv bolus) was dose-dependently attenuated by L-arginine. The results show that L-NNA is an efficacious and long-acting pressor agent and are consistent with the hypothesis that endogenous NO plays an important role in the regulation of blood pressure.