Fig. 5. (A ) The NO²-arginine dose dependently increased the dexmedetomidine (Dex)-induced sleep time of drug-naïve rats. NO²-arginine was administered 15 min before administration of dexmedetomidine (100 μg/kg intraperitoneally). * P < 0.01, n = 8. (B ) Acute administration of a dose of NO²-arginine that did not affect dexmedetomidine-induced sleep time did not reverse the tolerance to the hypnotic effect of dexmedetomidine (100 μg/kg). * P < 0.05 different from control, n = 8. (C ) Concurrent administration of NO²-arginine (0.4–4 μg · kg⁻¹· h⁻¹) with dexmedetomidine (5 μg · kg⁻¹· h⁻¹) for 7 days dose-dependently blocked the development of tolerance to the hypnotic effect of dexmedetomidine (100 μg/kg intraperitoneally). * P < 0.05 different from control, #P < 0.05 different from both control and dexmedetomidine tolerant group, n = 7–8. Treatment with only NO²-arginine (1.25 μg · kg⁻¹· h⁻¹; last column) did not affect dexmedetomidine-induced sleep time. N = 8. All values are mean ± standard error of 7–8 rats. LORR = loss of righting reflex.