Chronic anti-Thy-1 nephritis is aggravated in the nonclipped but not in the clipped kidney of Goldblatt hypertensive rats.
BACKGROUND
We have previously shown that renovascular hypertension does not inhibit healing of the acute Thy-1 nephritis. To test whether a chronic model of the Thy-1 nephritis is more susceptible to high blood pressure, the repetitive hit model was evaluated in rats with 2-kidney, 1-clip Goldblatt hypertension.


METHODS
Six weeks after initiation of 2-kidney, 1-clip hypertension, chronic Thy-1 glomerulonephritis was induced in hypertensive rats by four consecutive injections of rabbit antiserum in weekly intervals. Renal structure and function were examined two weeks after the last injection. Glomerular binding of rabbit IgG as well as expression of transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin (alpha-SMA) and cyclooxygenase (COX)-1 and -2 were evaluated by Western blotting.


RESULTS
Similar glomerular deposition of rabbit IgG was detected in normotensive rats and in both kidneys of Goldblatt hypertensive rats indicating similar delivery and binding of the heterologous antibody. Induction of the repetitive Thy-1 model significantly enhanced glomerular damage in the nonclipped kidney and increased albuminuria. Surprisingly, no glomerular damage developed in the clipped kidney of nephritic hypertensive rats. In contrast, increased glomerular volume and increased expression of TGF-beta, alpha-SMA as well as COX-1 and COX-2 were found in normotensive nephritic rats and in both kidneys of nephritic hypertensive rats.


CONCLUSIONS
Glomerular and tubulointerstitial damage of the chronic Thy-1 model is dramatically enhanced in the nonclipped kidneys of Goldblatt hypertensive rats. In contrast, the clipped kidney is completely protected from this immunological injury despite similar activation of glomerular cells, induction of TGF-beta, COX-1 and COX-2 and glomerular hypertrophy.
Wenzel
Ulrich O
UO
Division of Nephrology, Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany. wenzel@uke.uni-hamburg.de
Wolf
Gunter
G
Jacob
Ivonne
I
Thaiss
Friedrich
F
Helmchen
Udo
U
Stahl
Rolf A K
RA
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D006978:Hypertension, Renovascular / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007106:Immune Sera / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D009393:Nephritis / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D007106:Immune Sera; D007518:Isoantibodies; D007527:Isoenzymes; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; C035678:anti-Thy antibody; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat