Nitric oxide formation lowers norepinephrine‐induced intrahepatic resistance without major effects on the metabolism in the perfused rat liver

• Published in: Hepatology (Baltimore, Md.) Vol. 26; no. 1; pp. 147 - 154
• Main Authors: Weidenbach, H, Nussler, A K, Shu, Z, Adler, G, Beckh, K
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.1997; Wiley
• Subjects: Animals; Arginine - pharmacology; Bile - drug effects; Biological and medical sciences; Blotting, Western; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; In Vitro Techniques; Lactic Acid - metabolism; Lipopolysaccharides - pharmacology; Liver - drug effects; Liver - metabolism; Liver. Bile. Biliary tracts; Male; Nitric Oxide - physiology; Nitric Oxide Synthase - metabolism; Norepinephrine - pharmacology; omega-N-Methylarginine - pharmacology; Portal Pressure; Rats; Rats, Wistar; Time Factors; Vertebrates: digestive system; Measurement; Regional blood flow; Concentration factor; Rat; Digestive system; Secretion; Liver; Rodentia; Increase; Experimental study; Vertebrata; Mammalia; Vascular resistance; Animal; Nitric oxide; Norepinephrine; Circulatory system; Biological effect; Bile
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.510260120

Nitric oxide (NO) and norepinephrine are potent vasoactive agents that are involved in the control of portal blood flow. We have studied NO and norepinephrine in a non‐recirculated rat liver perfusion to analyze their influence on portal flow and hepatic metabolism. Animals were either pretreated with endotoxin (4 hours; 10 mg/kg intraperitoneally) to activate the inducible NO synthase (NOS2), or used without pretreatment for the constitutive NO synthase (NOS3). In both groups, portal flow, bile flow, bile secretion, and the sinusoidal bile acid uptake were reduced by norepinephrine with a simultaneous increase of glucose and lactate output. The addition of the substrate for NO synthesis, L‐arginine (0.5 mmol/L), to the perfusate markedly inhibited the effect of 0.1 μmol/L norepinephrine on portal flow from −2.6 ± 0.32 to 0.3 ± 0.1 mL/g/10 min in endotoxin‐treated animals, and from −2.9 ± 0.45 to 0.77 ± 0.29 mL/g/10 min in the untreated ones. In contrast, neither NO formation after L‐arginine supplementation nor inhibition of NO synthesis via the structural analogue (NG‐monomethyl‐L‐arginine [L‐NMMA]) changed cholestatic and glycogenolytic effects caused by norepinephrine. Only the sinusoidal bile acid uptake was reduced following increased NO formation. Thus, we conclude that endogenous NO formation prevents α‐catecholaminergic‐increased intrahepatic resistance without a major influence on the metabolic effects.