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In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the I n cirrhotic livers, increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension. 1 This increased resistance is determined in part by the architectural distortion of the hepatic structure caused by cirrhosis. However, substantial evidence shows that a dynamic component, caused by the active contraction of vascular and extravascular contractile cells, plays a major role in further increasing intrahepatic resistance. 2 This dynamic component of hepatic vascular resistance is believed to be the consequence of an imbalance between the vasodilator/vasoconstrictor forces that regulate hepatic vascular tone. 1 In addition, the hepatic vascular resistance of cirrhotic livers exhibits a hyperresponse to several vasoconstrictors, such as endothelin 1, 3 norepinephrine, 4 or leukotriene D 4 . 5 Nitric oxide blunts the response of the hepatic vascular bed to several vasoconstrictors, 6 and its production is decreased in the cirrhotic liver. It is therefore possible that an insufficient availability of NO 7 could account for the hyperresponse to vasoconstrictors observed in cirrhotic livers.In addition, it has been shown that the activation of G protein-coupled receptors, such as those for ␣ 1 -adrenergic agonists, vasopressin, or endothelin 1, stimulates release of arachidonic acid, leading to the formation of its vasoactive-derived metabolites, including prostaglandins (PGs), thromboxanes (TXs), and leukotrienes. [8][9][10] Cyclooxygenase (COX)

In cirrhotic livers, decreased nitric oxide (NO) bioavailability is a major factor increasing intrahepatic vascular tone. In several vascular disorders, an increase in superoxide (O 2 ؊ ) has been shown to contribute to reduced NO bioavailability through its reaction with NO to form peroxynitrite. This study was aimed to test the hypothesis that, in cirrhotic livers, increased