Changes in glomerular filtration rate and renal plasma flow in cirrhotic rats during converting enzyme inhibition.
During the development of cirrhosis ascites-edema, peripheral vasodilatation, hypotension and an increase of the plasma concentration of several neurohormones are frequently observed. Such complex changes in the hormonal profile hinders the assessment of the relative role of each in the pathophysiology of this disease. The purpose of this work was to evaluate in a rat model of experimental cirrhosis (phenobarbital/CCl4) the role of the renin-angiotensin system in the pre-ascitic stage of the disease using the converting enzyme inhibitor captopril. Cirrhotic rats showed diminished renal and hepatic perfusion. Compared to normal rats, glomerular filtration rate in cirrhotic rats was reduced from 0.75 +/- 0.11 to 0.42 +/- 0.06 mL/min/100 g BW, and renal plasma flow was reduced from 2.37 +/- 0.28 to 1.58 +/- 0.16 mL/min/100 g BW; the indocyanine green slope changed from -0.095 +/- 0.028 to -0.057 +/- 0.01; the plasma sodium concentration fell from 144 +/- 1.5 to 131 +/- 5.40 mEq/L (all < .05). The mean arterial pressure was not reduced in the cirrhotic rats. There was no ascites. Both the acute (25 mg i.v.) and chronic (25 mg i.p. daily plus 25 mg/L in drinking water) administration of captopril to cirrhotic rats induced an increase in glomerular filtration rate and renal plasma flow along with a steeper slope in indocyanine green decay (p < .05 for all three parameters) when compared to non-treated cirrhotic animals. No changes were observed in controls. In the balance studies, an increase in urinary volume along with a decrease in urinary osmolality was recorded in cirrhotic rats on chronic captopril treatment. In conclusion, our results show an activation of the renin-angiotensin system in these rats, as disclosed by the inhibition of the converting enzyme, as well as a possible interaction with ADH.
Ibarra
F R
FR
Laboratorio de Nefrologia Experimental, Instituto de Investigaciones Médicas Alfredo Lanari, Faculty of Medicine, Buenos Aires University, Argentina.
Galcerán
T
T
Oddo
E
E
Arrizurieta
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017595:Renal Plasma Flow / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril