Nitric oxide and vascular remodeling modulate hepatic arterial vascular resistance in the isolated perfused cirrhotic rat liver.
OBJECTIVE
Hepatic arterial resistance is modulated by the hepatic arterioles but the role of NO and vascular remodeling in hepatic arterial resistance in cirrhosis is unknown.


METHODS
Cirrhosis was induced by CCl(4) or BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were obtained from the hepatic artery in absence and presence of L-NMMA. Lumen-diameter, wall thickness and number of smooth muscle nuclei were quantitated in the arteries using image analysis.


RESULTS
Hepatic arterial resistance and the response to methoxamine were lower in cirrhosis compared to controls (p< or = 0.04) and lower in BDL compared to CCl(4) (p< or = 0.01). L-NMMA increased the response to methoxamine in CCl(4) (p=0.002) and BDL (p=0.05) but corrected the response only in CCl(4) (p=n.s. vs. control). Wall thickness and the number of smooth muscle nuclei were significantly smaller in cirrhosis compared to controls (p<0.05) and the number of nuclei was also lower in BDL compared to CCl(4) (p=0.005).


CONCLUSIONS
NO is the main modulator of hepatic arterial resistance in CCl(4) but not in BDL. Intrahepatic arterial remodeling is present in both cirrhotic models but is greater in BDL. This indicates a larger role of structural changes in the control of hepatic arterial resistance in BDL.
Zipprich
Alexander
A
Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA.
Loureiro-Silva
Mauricio R
MR
Jain
Dhanpat
D
D'Silva
Irita
I
Groszmann
Roberto J
RJ
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000818:Animals; D001652:Bile Ducts; D002251:Carbon Tetrachloride / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006499:Hepatic Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage; D009569:Nitric Oxide / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D009569:Nitric Oxide; D002251:Carbon Tetrachloride; D008729:Methoxamine