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. CONCLUSION: 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.
BACKGROUND: We have previously shown that renovascular hypertension does not inhibit healing of the acute Thy-1nephritis. To test whether a chronic model of the Thy-1nephritis 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-1glomerulonephritis was induced in hypertensiverats 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 hypertensiverats 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 hypertensiverats. 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 hypertensiverats. CONCLUSION: Glomerular and tubulointerstitial damage of the chronic Thy-1 model is dramatically enhanced in the nonclipped kidneys of Goldblatt hypertensiverats. 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.
Authors: Alex A Gutsol; Paula Blanco; Taben M Hale; Jean-Francois Thibodeau; Chet E Holterman; Rania Nasrallah; Jose W N Correa; Sergey A Afanasiev; Rhian M Touyz; Chris R J Kennedy; Dylan Burger; Richard L Hébert; Kevin D Burns Journal: PLoS One Date: 2022-02-17 Impact factor: 3.240