Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide.
Nitric oxide is a vasodilator tonically secreted by endothelial cells that is involved in the regulation of arteriolar tone. This study, which includes two protocols, was performed to investigate whether nitric oxide plays a role in the pathogenesis of arterial hypotension in cirrhosis with ascites. In protocol 1, the administration of increasing doses (25, 50, 250, 500 and 1,000 micrograms.kg-1.min-1) of the nitric oxide biosynthesis inhibitor N omega-nitro-L-arginine to 18 conscious rats with cirrhosis and ascites produced, at each dose tested, a significantly greater increase in arterial pressure than in 17 conscious control rats. At the lowest dose of N omega-nitro-L-arginine, arterial pressure significantly rose in cirrhotic rats but not in controls. In protocol 2, arterial pressure, estimated renal plasma flow, glomerular filtration rate and sodium excretion were measured in 12 cirrhotic rats with ascites and 10 control rats before and during the sequential infusion of previously selected doses of N omega-nitro-L-arginine (25, 50 and 250 micrograms.kg-1.min-1). Changes in arterial pressure reproduced those observed in protocol 1. In control rats, N omega-nitro-L-arginine caused a decrease in estimated renal plasma flow without affecting glomerular filtration rate or sodium excretion. In contrast, N omega-nitro-L-arginine administration to cirrhotic animals did not produce any appreciable renal vasoconstrictor effect, and it increased glomerular filtration rate and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Clària
J
J
Hormonal Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
Jiménez
W
W
Ros
J
J
Asbert
M
M
Castro
A
A
Arroyo
V
V
Rivera
F
F
Rodés
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries; D001160:Arterioles / Q000503:physiopathology; D001201:Ascites / Q000150:complications*; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium