Early events in ischemic renal failure in the rat: effects of antioxidant therapy.
Renal ischemia followed by two hours of reperfusion produces a complex form of acute renal failure characterized by a reduction in nephron filtration rate (SNGFR) and moderate proximal tubular damage. We have examined glomerular hemodynamics, SNGFR and histologic changes after renal ischemia and two hours of reperfusion in untreated (I) rats and rats pretreated with the antioxidant, probucol (IP). SNGFR decreased significantly by 47% in I rats. Reduction in SNGFR was primarily the result of a major decrease in the glomerular capillary hydrostatic pressure gradient, delta P, and a decrease in nephron plasma flow (SNPF). The glomerular ultrafiltration coefficient remained equal to control valves. In IP rats SNGFR was improved to values 89% of control rats due to higher values of delta P and SNPF. Histologic evidence of modest damage to cells of the proximal tubule was equal in both untreated and probucol treated ischemic animals. These studies demonstrate that: (a) primary reductions in nephron filtration rate at the glomerulus result from decreases in delta P and nephron plasma flow; b) pretreatment with the antioxidant, probucol, increases nephron plasma flow and SNGFR, and maintains more normal values for delta P; and c) tubular damage was equivalent in I and IP rats in spite of differences in SNGFR.
Department of Medicine, University of California, San Diego School of Medicine.
J E
JE
Bird
A P
AP
Evan
O W
OW
Peterson
R C
RC
Blantz
D000818:Animals; D000975:Antioxidants; D005919:Glomerular Filtration Rate; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D008297:Male; D009392:Nephrectomy; D010636:Phenols / Q000627:therapeutic use*; D011341:Probucol / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012077:Renal Artery / Q000502:physiology; D012079:Renal Circulation
D000975:Antioxidants; D010636:Phenols; D011341:Probucol