sults suggest that vascular NO production is higher in Nitric oxide (NO) is postulated to play a role in the cirrhotic rats than in PVL rats. This increased producpathogenesis of arterial vasodilation in chronic portal tion may contribute to the more marked abnormalities hypertension. This present study investigates the relain systemic hemodynamics seen in experimental cirrhotionship between systemic hemodynamics and the vassis as compared with PVL. (HEPATOLOGY 1996;24:947cular production of NO, as estimated by measuring cy-951.) clic guanosine monophosphate (cGMP) in aortic tissue in two models of chronic portal hypertension in the rat: the partial portal vein ligation (PVL) model and CCl 4 -Chronic portal hypertension is characterized by a hyperdyinduced cirrhosis. NOS was also examined by Western namic circulatory state with reduced systemic vascular resisblotting in aortic and mesenteric vessels. Sham-operated tance, increased plasma volume and cardiac output, and rats and rats given phenobarbital were used as controls.
marked portosystemic shunting. [1][2][3] Recently, several studies PVL rats and rats with cirrhosis and ascites showed a have been published investigating the role of nitric oxide typical pattern of a hyperdynamic circulatory state, (NO), a potent vasodilator factor synthesized in the arterial when compared with their respective controls: mean arwall, 4 in the pathogenesis of arterial vasodilation in experiterial pressure; PVL: 113 { 2 versus 124 { 2, P õ .01 and mental models of chronic portal hypertension. 5-10 Most of cirrhotics: 103 { 5 versus 130 { 4 mm Hg, P õ .01. Cardiac these investigations have been performed in two different index; PVL: 32 { 2 versus 26 { 1, P õ .01 and cirrhotics: models of portal hypertension in the rat, namely the stenosis 51 { 3 versus 30 { 1 mLrmin 01 r100 gm 01 , P õ .0001. Sysof the portal vein induced by partial portal vein ligation (PVL) temic vascular resistance; PVL: 3.7 { 0.1 versus 4.9 { 0.2, and the CCl 4 -induced cirrhosis. Although there are consider-P õ .01 and cirrhotics: 2.1 { 0.2 versus 4.4 { 0.2 mm able similarities, particularly with respect to the develop-Hgrmin 01 r100 g 01 , P õ .0001. Aortic cGMP was markedly ment of a hyperdynamic circulatory state, differences also increased in cirrhotic rats with ascites (728 { 83 fmol/ exist between these experimental models. First, they differ mg protein) as compared with phenobarbital-treated in the location of the increased resistance to the portal flow. controls (244 { 31 fmol/mg, P õ .
001). This increase was
The PVL model is a model of prehepatic portal hypertension abolished by chronic administration of N v -nitro-L-argibecause the increased resistance is located in the portal vein nine methyl ester. By contrast, PVL rats had an aortic outside the liver. In contrast, carbon tetrachloride-induced cGMP concentration similar to sham-operated controls cirrhosis is a model of intrahepatic portal hypertension be-(282 { 16 fmol/mg vs. 274 { 33 fmol/mg, P Å not significause the increased resistance is located in the hepatic sinucant) and significantly lower than that found in cirrhotic soids. Second, the development of portal-systemic shunting rats with ascites. Expression of cirrhotic aortic endothediffers substantially in the PVL model (ú90%) from the cirlial nitric oxide synthase (eNOS) was increased but PVL rhotic model (variable, but usually around 10%). 11 Third, ciraortic eNOS did not differ from that of controls, whereas rhotic rats have a much more marked activation of vasoconthe mesenteric eNOS was increased in both PVL and strictor systems than PVL rats. 12 Finally, although PVL rats cirrhotic rats as compared with the controls. These reshow mild sodium retention early after ligation of the portal vein, 9 which is responsible for the increase in plasma volume, they never develop ascites. By contrast, cirrhotic rats consis-Abbreviations: PVL, portal vein ligation; cGMP, cyclic guanosine monophosphate; eNOS, tently have more avid sodium and water retention coincident endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; MAP, mean arterial with ascites formation and the appearance of abnormalities pressure; CO, cardiac output; CI, cardiac index; SVR, systemic vascular resistance; ANP, in systemic hemodynamics. 13,14 Therefore, in spite of the exisatrial natriuretic peptide.