Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination Export

@article{citeulike:3842906, abstract = {Angiotensin II accelerates and renin-angiotensin system blockade halts progression; blockade with high doses even reverses established glomerulosclerosis. Aldosterone also accelerates progression of glomerulosclerosis, partially independently of angiotensin II. The purpose of this study was to assess the relative ability of an angiotensin receptor type 1 (AT1) blocker, a mineralocorticoid receptor blocker, and their combination to reverse glomerulosclerosis. Sprague-Dawley rats were subjected to subtotal renal ablation (SNX) or sham operation. Eight weeks after surgery, they were either euthanized or allocated to treatment with vehicle, losartan, spironolactone, their combination, or unspecific antihypertensive treatment (dihydralazine) for 4 wk. Renal morphology was evaluated by stereology in tissues obtained using pressure-controlled perfusion fixation. Systolic blood pressure was significantly higher in SNX compared with sham-operated animals and decreased in all treatment groups. Compared with wk 8 after SNX, the glomerulosclerosis index (GSI) had increased further by week 12 in the vehicle- and dihydralazine-treated groups but was significantly lowered in the SNX+losartan as well as in the SNX+losartan+spironolactone groups and had not progressed further in the SNX+spironolactone group. The study confirms the partial regression of established glomerulosclerosis in subtotally nephrectomized rats after high-dose AT1 receptor blockade. Nonhyperkalemic doses of spironolactone prevented the increase but failed to decrease the GSI below the 8-wk level and preserved podocyte numbers. Combining the AT1 blocker with mineralocorticoid receptor blockade failed to further increase the regression of glomerulosclerosis. 10.1152/ajprenal.00065.2008}, author = {Piecha, Grzegorz and Koleganova, Nadezda and Gross, Marie-Luise and Geldyyev, Aman and Adamczak, Marcin and Ritz, Eberhard}, citeulike-article-id = {3842906}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajprenal.00065.2008}, citeulike-linkout-1 = {http://ajprenal.physiology.org/cgi/content/abstract/295/1/F137}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18434388}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18434388}, doi = {10.1152/ajprenal.00065.2008}, journal = {Am J Physiol Renal Physiol}, keywords = {aldosterone, arb, rat, snx}, month = {July}, number = {1}, pages = {F137--144}, posted-at = {2009-01-02 16:27:13}, priority = {2}, title = {Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination}, url = {http://dx.doi.org/10.1152/ajprenal.00065.2008}, volume = {295}, year = {2008} }

TY - JOUR ID - citeulike:3842906 L3 - citeulike-article-id:3842906 N2 - Angiotensin II accelerates and renin-angiotensin system blockade halts progression; blockade with high doses even reverses established glomerulosclerosis. Aldosterone also accelerates progression of glomerulosclerosis, partially independently of angiotensin II. The purpose of this study was to assess the relative ability of an angiotensin receptor type 1 (AT1) blocker, a mineralocorticoid receptor blocker, and their combination to reverse glomerulosclerosis. Sprague-Dawley rats were subjected to subtotal renal ablation (SNX) or sham operation. Eight weeks after surgery, they were either euthanized or allocated to treatment with vehicle, losartan, spironolactone, their combination, or unspecific antihypertensive treatment (dihydralazine) for 4 wk. Renal morphology was evaluated by stereology in tissues obtained using pressure-controlled perfusion fixation. Systolic blood pressure was significantly higher in SNX compared with sham-operated animals and decreased in all treatment groups. Compared with wk 8 after SNX, the glomerulosclerosis index (GSI) had increased further by week 12 in the vehicle- and dihydralazine-treated groups but was significantly lowered in the SNX+losartan as well as in the SNX+losartan+spironolactone groups and had not progressed further in the SNX+spironolactone group. The study confirms the partial regression of established glomerulosclerosis in subtotally nephrectomized rats after high-dose AT1 receptor blockade. Nonhyperkalemic doses of spironolactone prevented the increase but failed to decrease the GSI below the 8-wk level and preserved podocyte numbers. Combining the AT1 blocker with mineralocorticoid receptor blockade failed to further increase the regression of glomerulosclerosis. 10.1152/ajprenal.00065.2008 IS - 1 JF - Am J Physiol Renal Physiol EP - 144 TI - Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination VL - 295 SP - F137 KW - aldosterone KW - arb KW - rat KW - snx AU - Piecha, Grzegorz AU - Koleganova, Nadezda AU - Gross, Marie-Luise AU - Geldyyev, Aman AU - Adamczak, Marcin AU - Ritz, Eberhard PY - 2008/07/01/ UR - http://dx.doi.org/10.1152/ajprenal.00065.2008 ER -