Intraportal administration of glyceryl trinitrate or nitroprusside exerts more systemic than intrahepatic effects in anaesthetised cirrhotic rats

Background/Aims: Increased intrahepatic vascular tone can be pharmacologica lly manipulated in isolated cirrhotic livers. Intrahepatic endothelial dysf unction may lead to a decreased production of the potent endogenous vasodil ator nitric oxide in cirrhotic livers. The aims of the study were to determ ine whether portal pressure can be lowered in vivo by injecting nitric oxid e donors glyceryl trinitrate or nitroprusside directly in the portal vein a nd whether this is related to a decrease in intrahepatic resistance. Methods: In anaesthetised CCl4 cirrhotic rats, intraportal doses of glycery l trinitrate 0.5, 1 or 5 mu g/kg/min or nitroprusside 1, 5 or 10 mu g/kg/mi n did not decrease portal pressure but only arterial pressure. Systemic and splanchnic haemodynamics were measured before and during 15 min intraporta l infusion of glyceryl trinitrate 10 mu g/kg/min or nitroprusside 20 mu g/k g/min. Results: Glyceryl trinitrate decreased portal pressure from 14.0+/-1.1 to 1 1.8+/-1.4 mm Hg, splanchnic perfusion pressure from 102+/-10 to 74+/-5 mm H g and portal sinusoidal flow from 2.11+/-0.38 to 1.70+/-0.35 ml/min/g liver (all p<0.05), Nitroprusside did not decrease portal pressure significantly but led to a reduction of the splanchnic perfusion pressure (104+/-9 to 66 +/-7 mm Hg) and the portal sinusoidal flow (2.39+/-0.50 to 1.77+/-0.31 ml/m in/g liver; all p<0.05). Portal sinusoidal resistance was not altered by ei ther drug. Conclusions: Intraportal infusion of nitric oxide donors decreased arterial pressure more than portal pressure. Portal sinusoidal resistance remained unaffected, but the liver parenchyma became less perfused with high doses. The systemic effects of nitric oxide donating drugs prevailed.