NITRIC-OXIDE MODULATES HEPATIC VASCULAR TONE IN NORMAL RAT-LIVER

This study investigated whether nitric oxide (NO) plays a role in the intrahepatic portal circulation in normal rat livers perfused in situ. N-omega-nitro-L-arginine (NNA), a specific NO biosynthesis inhibitor, significantly increased baseline portal pressure compared with contro ls (P < 0.05). Concentration-effect curves to norepinephrine (NE) were performed. Perfusate flow was maintained as constant, and perfusion p ressure was continuously measured. NNA markedly enhanced the responsiv eness to NE. This effect was abolished by the addition of L-arginine, a specific NO substrate. Presence of indomethacin did not alter the re sponse to NE. The response to NE in the presence of indomethacin and N NA was significantly more than the response to NE in the presence of N NA alone. In vivo, intraportal infusion of NNA significantly enhanced the portal pressure compared with vehicle. This study demonstrates tha t NO contributes to the basal vascular tone and attenuates the respons e to NE in intrahepatic portal vascular bed of normal rats. These resu lts support a functional role of NO in the regulation of the intrahepa tic portal circulation in normal rats. This study also suggests a syne rgistic, albeit limited, role of prostacyclin in the intrahepatic circ ulation.