Impaired responsiveness to angiotensin II in experimental cirrhosis: role of nitric oxide.
Impaired vascular responsiveness to angiotensin II is a common feature in human cirrhosis with ascites. The aim of this study was to investigate whether vascular reactivity to angiotensin II is also decreased in rats with carbon tetrachloride-induced cirrhosis and ascites and to assess the role of endogenous nitric oxide in this abnormality. Increasing doses of angiotensin II (from 31 to 500 ng.kg-1.min-1) induced significantly smaller increases in total peripheral resistance in conscious cirrhotic rats with ascites (n = 8) than in control animals (n = 9) at each dose tested. A reduced response to angiotensin II was also observed in vitro in aortic rings of rats with cirrhosis and ascites compared with that in control aortic rings (maximal response: 104 +/- 16 mg vs. 204 +/- 18 mg; p < 0.001). This in vitro hyporesponsiveness to angiotensin II in aortic rings of cirrhotic rats with ascites was reversed on endothelium denudation or nitric oxide synthesis inhibition with N omega-nitro-L-arginine but was not influenced by cyclooxygenase inhibition with indomethacin. In conclusion, this study shows reduced vascular reactivity to angiotensin II in carbon tetrachloride-induced cirrhosis with ascites and indicates that this abnormality is mediated by nitric oxide.
Castro
A
A
Hormonal Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
Jiménez
W
W
Clària
J
J
Ros
J
J
Martínez
J M
JM
Bosch
M
M
Arroyo
V
V
Piulats
J
J
Rivera
F
F
Rodés
J
J
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar
D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine