Angiotensin II modulates atrial natriuretic factor-induced natriuresis in cirrhosis with ascites.
Resistance to the natriuretic action of atrial natriuretic factor (ANF) in cirrhosis with ascites has been correlated with rising levels of antinatriuretic factors, such as renin, angiotensin II (AII), and aldosterone, as well as increased sympathetic nerve activity. To determine whether AII can serve as a mediator rather than only as a marker of the antinatriuresis, a nonpressor dose of AII (5 ng/kg/min) was given during an ANF infusion in eight patients with cirrhosis and ascites who responded to ANF infusion with a natriuresis. Patients were maintained in metabolic balance and measurements of para-aminohippuric acid, inulin, and lithium clearance were taken before and during infusion of ANF with or without AII. Atrial natriuretic factor infusion was associated with a natriuretic response accompanied by an increase in glomerular filtration rate, filtration fraction, and lithium clearance compared with baseline. The addition of AII was associated with a return of the glomerular filtration rate to baseline, with no change in filtration fraction. This was reversible on withdrawal of AII infusion. Natriuresis induced by ANF occurred despite baseline elevations of the renin angiotensin aldosterone system and was associated with an increase in distal delivery of sodium and a decrease in fractional reabsorption of distally delivered sodium as estimated by lithium clearance parameters. Angiotensin II infusion exerted effects on both proximal and distal nephron sites to abrogate ANF-induced natriuresis. These results suggest that AII may serve as a mediator as well as a marker of resistance to the natriuretic effect of ANF in patients with cirrhosis and ascites.(ABSTRACT TRUNCATED AT 250 WORDS)
Tobe
S W
SW
Department of Medicine, University of Toronto, Ontario, Canada.
Blendis
L M
LM
Morali
G A
GA
Warner
L C
LC
Logan
A G
AG
Skorecki
K L
KL
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000502:physiology*; D001201:Ascites / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology*
D000804:Angiotensin II; D009320:Atrial Natriuretic Factor