Renovascular hypertension does not influence repair of glomerular lesions induced by anti-thymocyte glomerulonephritis.
BACKGROUND
Systemic hypertension is a risk factor for progression of renal disease. However, it is not clear whether hypertension has an effect on healing or regression of immune-mediated glomerular damage. To evaluate this effect, we applied a model of glomerulonephritis in rats with two-kidney, one-clip hypertension and studied the effect of hypertension on the healing process of this nephritis.


METHODS
The anti-thymocyte serum (ATS) glomerulonephritis was induced in rats six weeks after initiation of two-kidney, one-clip hypertension, when blood pressure was already increased. Renal structure and function were examined six weeks later. Glomerular expression of alpha smooth muscle actin, the cell cycle inhibitor p27Kip1, and transforming growth factor-beta (TGF-beta) was evaluated by Western blotting. Glomerular proliferation, monocyte infiltration, and fibronectin were examined by immunohistochemistry.


RESULTS
Decreased survival, an increase of proteinuria, as well as increased glomerular and tubulointerstitial damage, were found in hypertensive rats compared with normotensive rats. Expression of fibronectin, alpha-smooth muscle actin, TGF-beta, and p27Kip1 was increased in the nonclipped kidney. Complete healing of the glomerular changes associated with the nephritis occurred in normotensive nephritic rats. Surprisingly, complete healing of the nephritis was also found in the clipped as well as nonclipped kidneys of renovascular hypertensive rats. No significant differences could be found for survival, proteinuria, glomerular size, proliferation, monocyte/macrophage infiltration, sclerosis, tubulointerstitial damage, as well as expression of alpha-smooth muscle actin, TGF-beta, fibronectin, and p27Kip1 between hypertensive rats with and without nephritis.


CONCLUSIONS
These data demonstrate that renovascular hypertension does not influence healing of the glomerular lesions in the anti-thymocyte serum nephritis. This is a rather surprising observation and leaves the question open of which role, in fact, blood pressure may have on the reparative phase of an acute glomerulonephritis, or whether its role depends on the type of glomerulonephritis.
Wenzel
U O
UO
Division of Nephrology, Department of Medicine, and Department of Pathology, University Hospital Hamburg, Germany. wenzel@uke.uni-hamburg.de
Wolf
G
G
Thaiss
F
F
Helmchen
U
U
Stahl
R A
RA
D000818:Animals; D001794:Blood Pressure; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D006977:Hypertension, Renal / Q000276:immunology / Q000473:pathology*; D006984:Hypertrophy; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009000:Monocytes / Q000276:immunology; D011507:Proteinuria / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000032:analysis; D025521:Tumor Suppressor Proteins
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D007074:Immunoglobulin G; D008869:Microtubule-Associated Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27