A comparison of the effects of converting-enzyme inhibition and protein restriction in experimental nephrosis.

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.

Naphthylphthalamic acid-binding sites in cultured cells from Nicotiana tabacum.

Naphthylphthalamic acid (NPA), an inhibitor of polar auxin transport, binds with high affinity to membrane preparations from callus and cell suspension cultures derived from Nicotiana tabacum (K d approx. 2·10(-9) M). The concentration of membrane-bound binding sites is higher in cell suspension than in callus cultures. The binding of NPA to these sites seems to be a simple process, in contrast to the binding of the synthetic auxin naphthylacetic acid (1-NAA) to membrane preparations from callus cultures, which is more complex (A.C. Maan et al., 1983, Planta 158, 10-15). Naphthylacetic acid, a number of structurally related compounds and the auxin-transport inhibitor triiodobenzoic acid were all able to compete with NPA for the same binding site with K d values ranging from 10(-6) to 10(-4) M. On the other hand, NPA was not able to displace detectable amounts of NAA from the NAA-binding site. A possible explantation is the existence of two different membrane-bound binding sites, one exclusively for auxins and one for NPA as well as auxins, that differ in concentration. The NPA-binding site is probably an auxin carrier.

Converting enzyme inhibition and progressive glomerulosclerosis in the rat.

The effect of converting enzyme inhibition (CEI) by captopril (CAP, 500 mg/liter drinking water) on the development and progression of glomerulosclerosis (GS) was studied in six groups of male uninephrectomized (UN) Wistar rats. In group A, treated with CAP for four to five weeks after UN, a reduction in systolic blood pressure (SBP), filtration fraction and glomerular volumes was found as compared to control group B. Long-term treatment with CAP for eight months after UN (group C) resulted in lowering of SBP with 30 mm Hg, a low level of proteinuria and low incidence of GS (0 to 1.5%) as compared to control rats (group D), with SBP of 131 +/- 4 mm Hg, proteinuria up to 103 to 509 mg/day and 9.1 to 29.7% GS at eight months after UN. Groups E and F were followed without therapy up to seven months after UN, at which time a high level of proteinuria was present. CAP therapy then started in group E, did not reduce SBP, proteinuria and GS at 11 months after UN relative to control group F. This study shows that early CEI prevents progressive proteinuria and GS in rats after UN and is associated with a reduction in SBP, filtration fraction and glomerular volume. Once high levels of proteinuria and GS have developed in rats after UN, CEI has no effect on SBP nor on the progression of GS and proteinuria.