The involvement of nitric oxide (NO) in the vascular escape from norepinephrine (NE)-induced vasoconstriction was investigated in the hepatic arterial vasculature of anesthetized cats. The hepatic artery was perfused by free blood flow or pump-controlled constant-flow, and NE (0.15 and 0.3 µg · kg¹ · min¹, respectively) was infused through the portal vein. In the free-flow perfusion model, the NE-induced hepatic vasoconstriction recovered from the maximum point of the constriction, resulting in 36.6 ± 5.9% vascular escape. Blockade of NO formation with N-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg ipv) potentiated NE-induced maximum vasoconstriction, and the potentiation was reversed by L-arginine (75 mg/kg ipv). Furthermore, NE-induced vasoconstriction became more stable after L-NAME, resulting in an inhibition of vascular escape (7.5 ± 3.3%), and the inhibition was reversed by L-arginine (23.0 ± 6.4%). Similar potentiation of NE-induced vasoconstriction and inhibition of hepatic vascular escape by L-NAME (40.4 ± 4.3% control vs. 10.2 ± 3.7% post-L-NAME escape) and the reversal by L-arginine were also observed in the constant-flow perfusion model. The data suggest that NO is the major endogenous mediator involved in the hepatic vascular escape from NE-induced vasoconstriction.