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Am J Physiol Gastrointest Liver Physiol 284: G567-G574, 2003. First published December 18, 2002; doi:10.1152/ajpgi.00452.2002
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Vol. 284, Issue 4, G567-G574, April 2003

Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas

Mauricio R. Loureiro-Silva1, Gregory W. Cadelina2, and Roberto J. Groszmann1,2

1 Digestive Diseases Section, Yale University School of Medicine, New Haven 06520; and 2 Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, West Haven, Connecticut 06516

Intrahepatic nitric oxide (NO) production is decreased in cirrhotic livers. Our objective was to identify, in cirrhotic rat livers, intrahepatic vascular segments where the deficit of NO facilitates the effect of vasoconstrictors. By using a modified rat liver perfusion system with measurement of both the perfusion and sinusoidal (wedged hepatic vein) pressures, we studied the effect of the NO synthase blocker Nomega -nitro-L-arginine (L-NNA) on the response to methoxamine (alpha 1-adrenoreceptor agonist) in different segments of the intrahepatic circulation of normal and cirrhotic rat livers. L-NNA enhanced the presinusoidal, sinusoidal, and postsinusoidal responses to methoxamine in normal livers as well as the presinusoidal response in cirrhotic livers. However, L-NNA did not change the already enhanced sinusoidal/postsinusoidal response to methoxamine in cirrhotic livers. The postsinusoidal response to methoxamine was higher in cirrhotic rats with ascites than in those without ascites. We concluded that NO modulates the presinusoidal, sinusoidal, and postsinusoidal vascular tone in normal livers. NO production in cirrhotic rat livers is severely impaired in the sinusoidal and postsinusoidal areas but is preserved in the presinusoidal area, as evidenced by its normal response to L-NNA. We speculate that an increased postsinusoidal response to catecholamines may participate in the genesis of ascites in cirrhosis.

ascites; liver microcirculation; rat liver perfusion; nitric oxide synthase; wedged hepatic venous pressure


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