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.
Beukers
J J
JJ
Department of Pathology, State University of Leiden, The Netherlands.
van der Wal
A
A
Hoedemaeker
P J
PJ
Weening
J J
JJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D005921:Glomerulonephritis / Q000188:drug therapy*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril