Beukers J J, Hoedemaeker P J, Weening J J
Department of Pathology, University of Leiden, The Netherlands.
Lab Invest. 1988 Nov;59(5):631-40.
We compared the effects of protein restriction and converting-enzyme inhibition by captopril (CAP) on urinary protein excretion (UP) and progressive glomerular sclerosis (GS) in an experimental model of nephrosis induced in rats by a single injection of Adriamycin (ADR) at a dose of 3 mg/kg. Two isocaloric diets with a 6% and 22% (NP) protein content were used. Experimental groups were started on NP, on NP plus CAP (500 mg/liter) or on an isocaloric diet with a 6% protein content at day 2 after ADR injection and followed for 38 days. According to a cross-over design, groups were then switched to the alternative diet or maintained on the original diet, whereas in one CAP-treated group CAP treatment was stopped. All groups were followed for another 34 to 42 days and then sacrificed. Results showed that UP and the incidence of GS were significantly reduced in groups on the isocaloric diet with a 6% protein content during the full length or the second half of the observation period. In contrast, CAP had no effect on UP or on the incidence of GS, although systolic blood pressure was significantly reduced. Renal function studies performed in separate groups on the same regimes at 5 weeks after induction of ADR nephrosis, showed that LP had lowered glomerular filtration rate numerically and renal plasma flow significantly, whereas CAP was found to have no effect on glomerular filtration rate and renal plasma flow. Glomerular volumes were increased in proteinuric rats on both NP diet and NP diet with CAP treatment. The present study confirms earlier reports that in ADR-nephrotic rats, protein restriction attenuates UP and GS without affecting systolic blood pressure, whereas converting-enzyme inhibition does not have this beneficial effect although systolic blood pressure is lowered. GS seems to be related to glomerular extension and hypertrophy. The effect of protein restriction may be partially hemodynamically mediated by afferent vasoconstriction, resulting in a decrease in glomerular filtration rate and a reduction in protein flux across the ADR-induced large pore defects.
