In:
Diabetes, American Diabetes Association, Vol. 50, No. 11 ( 2001-11-01), p. 2619-2624
Abstract:
A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (Palb) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg · kg−1 · day−1. Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of Palb in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced Palb significantly in concentration ranges from 10−6 to 10−14 mol/l compared with results in control glomeruli. The effect on Palb may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the Palb defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
DOI:
10.2337/diabetes.50.11.2619
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2001
detail.hit.zdb_id:
1501252-9
