Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome.
Functional and morphologic measurements were performed in Munich-Wistar rats after a single central venous injection of puromycin aminonucleoside (PA) or saline vehicle (sham). During phase I, PA rats exhibited overt nephrotic syndrome and impaired glomerular filtration, primarily due to a reduction in the glomerular capillary ultrafiltration coefficient. The morphologic counterpart of the latter consisted of effacement of glomerular epithelial cell foot processes and decrease in the number of filtration slit diaphragms. Administration of the angiotensin I converting enzyme inhibitor (CEI) enalapril to PA rats did not ameliorate glomerular dysfunction. During phase II, PA rats exhibited spontaneous resolution of proteinuria, impaired function, and morphologic abnormalities. However, PA rats now demonstrated marked glomerular capillary hypertension and continued, albeit lesser, reductions in the ultrafiltration coefficient. Concurrent CEI administration modestly lowered systemic arterial pressure, and normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. Additional rats were studied during phase III, 70 wk after injection. In PA rats, prior glomerular hypertension was associated with development of recurrent proteinuria and extensive glomerular sclerosis, whereas concurrent CEI administration limited these parameters to values comparable to those in sham rats. Glomerular hypertension thus may explain the development of glomerular sclerosis and renal failure long after an episode of acute glomerular injury.
Anderson
S
S
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Diamond
J R
JR
Karnovsky
M J
MJ
Brenner
B M
BM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D005921:Glomerulonephritis / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D009404:Nephrotic Syndrome / Q000473:pathology*; D011507:Proteinuria / Q000209:etiology; D011692:Puromycin Aminonucleoside; D051381:Rats; D011919:Rats, Inbred Strains
D011692:Puromycin Aminonucleoside; D004656:Enalapril