Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas.
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 N(omega)-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.
Loureiro-Silva
Mauricio R
MR
Digestive Diseases Section, Yale University School of Medicine, New Haven 06520, USA.
Cadelina
Gregory W
GW
Groszmann
Roberto J
RJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D008729:Methoxamine