Increased platelet-derived growth factor in the kidneys of cyclosporin-treated rats.
We have examined the histological changes and the distribution of immunoreactive platelet-derived growth factor (PDGF) in the kidneys of Sprague-Dawley rats injected with cyclosporin A (CsA, 25 mg/kg/day). Control rats were injected with the olive oil vehicle alone. Groups of rats were killed after 1, 2, 3, 4 weeks of injection and 8 weeks after a 4 week period of injection. Additional controls included groups of rats injected with different doses of CsA and a group of rats subjected to chronic renal ischemia by partial of the aorta. CsA-treated rats gained weight more slowly than olive oil-treated controls (45%, P < 0.05). In rats injected with CsA, a significant increase in serum creatinine concentration (64 +/- 2 mumol/liter vs. 39 +/- 1 mumol/liter, P < 0.01) and a reduction in creatinine clearance rates (0.23 +/- 0.07 ml/min/100 g body wt vs. 0.43 +/- 0.07 ml/min/100 g body wt, P < 0.01) occurred after 3 weeks. After 1 week of CsA treatment, segments of the walls of some afferent and intralobular arterioles were thickened and stained strongly by the periodic acid Schiff (PAS) procedure. Immunostainable PDGF-BB and PDGF-AB were detected within short segments of the afferent and intralobular arterioles of the kidneys of CsA-treated rats and in the kidneys subjected to renal ischemia but not in tissue from other control animals. No PAS staining or immunostaining was evident in CsA treated kidneys eight weeks after the discontinuation of treatment. We conclude that CsA-induced ischemia results in increased accumulation of PDGF in the walls of renal arterioles.
Shehata
M
M
Sheffield Kidney Institute, Northern General Hospital NHS Trust, England, United Kingdom.
el Nahas
A
A
Barkworth
E
E
Cope
G H
GH
Raftery
A T
AT
D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010982:Platelet-Derived Growth Factor; D016572:Cyclosporine