Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats.
OBJECTIVE
Recent studies suggest that production of nitric oxide is increased in cirrhosis. This study determines to what extent this increased production contributes to arterial vasodilation and hyperdynamic circulation in cirrhosis.


METHODS
Mean arterial pressure (MAP), cardiac index, and systemic vascular resistance (SVR) were determined in cirrhotic rats with ascites undergoing long-term treatment with different doses of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (3 mg or 0.5 mg.kg-1.day-1). Untreated cirrhotic rats with ascites and controls were also studied. The vascular production of NO was estimated by the aortic concentration of guanosine 3',5'-cyclic monophosphate (cGMP).


RESULTS
Untreated cirrhotic rats had significantly lower MAP and SVR and higher cardiac index and aortic cGMP concentration than controls. When administrated to cirrhotic rats, an L-NAME dose of 3 mg.kg-1.day-1 induced a reduction of cGMP concentration less than normal levels. In these rats, MAP and SVR increased to greater than and cardiac index decreased to less than values in controls. By contrast, cirrhotic rats treated with 0.5 mg.kg-1.day-1 L-NAME had similar aortic cGMP concentrations as controls, suggesting a normalization of NO production. This was associated with a normalization of MAP, cardiac index, and SVR and a reduction in the elevated plasma renin activity and vasopressin concentration.


CONCLUSIONS
Normalization of vascular NO production corrects systemic hemodynamic abnormalities in cirrhotic rats with ascites.
Niederberger
M
M
Department of Medicine, University of Colorado School of Medicine, Denver, USA.
Martin
P Y
PY
Ginès
P
P
Morris
K
K
Tsai
P
P
Xu
D L
DL
McMurtry
I
I
Schrier
R W
RW
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000737:chemistry; D001794:Blood Pressure; D006152:Cyclic GMP / Q000032:analysis; D006439:Hemodynamics; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D014655:Vascular Resistance; D014664:Vasodilation; D014667:Vasopressins / Q000097:blood
D014667:Vasopressins; D009569:Nitric Oxide; D001120:Arginine; D012083:Renin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester