Nitric oxide-mediated effects on liver blood flow

We investigated whether blockade of nitric oxide synthase by the arginine analog L-NAME could affect peripheral liver blood flow (PLBF) or hepatocyte integrity (serum ALT) in either a control series or in a series subjected to mild reduction of liver blood flow by temporary clamping of the hepatic artery (HA). Anesthetized rats were arranged for mean arterial pressure (MAT) recordings via a carotid artery, drug injections, and blood sampling via a jugular vein, and monitoring of PLBF using a laser Doppler flowmeter. In series 1, the rats received either L-NAME (30 mg/kg i.v.) or NaCl. L-NAME caused a significant decrease in PLBF and an increase in MAP compared to NaCl; ALT did not differ. In series 2, L-NAME (30 mg/kg i.v.) or NaCl was administered at the beginning of the experiment. After 60 minutes of equilibration, the HA was clamped for 60 minutes then unclamped for another 60 minutes. As in series 1, the L-NAME group had significantly lower PLBF and higher MAP than the NaCl group. Occlusion of the HA resulted in significantly greater reduction in PLBF in the NaCl versus the L-NAME group. Upon unclamping, there was no difference in ALT levels, PLBF, or MAP. To conclude, NO displayed a positive tonic effect on liver blood flow, reduction of which with L-NAME did not aggravate mild ischemia/reperfusion injury in this model.