Renin-angiotensin system, blood pressure homeostasis and renal function in galactosamine-induced fulminant hepatic failure in the guinea pig.
Arterial blood pressure, renal function and plasma concentrations of renin and renin substrate (angiotensinogen) were investigated in guinea pigs subjected to galactosamine-induced (1 g/kg i.v.) liver cell necrosis. Blood pressure declined continuously by 50% during a follow-up period of 72 h which was associated with a decrease in diuresis and natriuresis to 36 and 31%, respectively. Simultaneously, plasma renin concentration increased 30-fold indicating marked reduction of renal perfusion, while plasma renin substrate concentration fell to 6% of the baseline level. There was microscopic evidence of oligemic circulatory renal damage characterized by acute proximal tubular necrosis with concomitant tubular dilatation. Short-term infusion of homologous renin substrate-enriched plasma, derived from nephrectomized animals, was followed by marked increase in mean arterial blood pressure from 34 +/- 9 to 77 +/- 7 mm Hg accompanied by marked diuresis and natriuresis. Renin substrate depletion following galactosamine-induced fulminant liver failure may represent impaired hepatic biosynthesis as well as increased renin substrate consumption due to excessive renin secretion. Angiotensinogen repletion has a beneficial effect on both renal function and blood pressure probably due to marked generation of the potent vasoconstrictor angiotensin II which consequently inhibits renin secretion. These observations strongly support the suggestion that the renin-angiotensin system is of major importance to cardiovascular homeostasis in acute liver failure.
D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D005688:Galactosamine; D006168:Guinea Pigs; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000503:physiopathology*; D008107:Liver Diseases / Q000097:blood / Q000503:physiopathology*; D008297:Male; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System
D000808:Angiotensinogen; D005688:Galactosamine; D012083:Renin