Cause of variable therapeutic efficiency of angiotensin converting enzyme inhibitor on glomerular lesions.
We tested the effect of angiotensin I converting enzyme inhibitor (ACEI) on established glomerular sclerosis. Starting eight weeks after subtotal nephrectomy (sNPX), rats were given enalapril for four weeks in a dose of 50 (Group II, N = 5) or 200 mg/liter drinking water (Group III, N = 5). A third group of sNPX rats not given ACEI served as control (Group I, N = 10). Glomerular sclerosis index (S1, 0 to 4 scale) was assessed three-dimensionally on serial thin sections for individual glomeruli at biopsy (Bx, 8 weeks), and divided into four different ranks of severity and compared to autopsy (Ax, 12 weeks). In Group I control rats, 48% of the glomeruli at Bx had SI between 0 and 1 (rank 1, average: 0.49 +/- 0.06), 36% between 1 and 2 (rank 2, average: 1.53 +/- 0.06), 9% between 2 and 3 (rank 3, average: 2.45 +/- 0.12) and 7% between 3 and 4 (rank 4, average: 3.54 +/- 0.10). Glomeruli of the same rats at Ax were ranked according to severity of sclerosis, and then divided into percentile groups, corresponding to the percent of distribution at Bx. The 48% least sclerotic glomeruli at Ax had average SI of 0.69 +/- 0.08, the next 36% 2.58 +/- 0.11, and next 9% 3.97 +/- 0.02 and the most sclerotic 7% 4.00 +/- 0.00. Thus, sclerosis advanced during the last four weeks after biopsy in all glomeruli, with more accelerated progression occurring toward later stages of sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
M
M
Ikoma
T
T
Kawamura
Y
Y
Kakinuma
A
A
Fogo
I
I
Ichikawa
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000008:administration & dosage / Q000627:therapeutic use*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood
D004656:Enalapril; D012964:Sodium; D011188:Potassium