BACKGROUND: Pleiotropic effects of statins represent potential mechanisms for the treatment of end organ damage in hypertension. This study has investigated the effects of rosuvastatin (10 mg/kg/day) on renal function impairment, glomerulosclerosis and tubulointerstitial fibrosis in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rat. METHODS: Rats were implanted with DOCA strips (200 mg/kg) on 1 week after unilateral nephrectomy. Rats received a controlled diet with or without rosuvastatin. Three weeks after DOCA implantation, systolic blood pressure (SBP) was measured by tail-cuff method. The glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome stain. The tumour necrosis factor (TNF-alpha), interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), monocyte chemoattractant protein1 (MCP1), intercellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) were determined by real-time polymerase chain reaction. The expression of ED-1, transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) was determined in the kidney by immunoblotting and immunohistochemistry. RESULTS: In DSH rats, SBP was increased, which was not affected by rosuvastatin treatment. Creatinine clearance was decreased while urinary albumin excretion ratio was increased in DSH rats compared with controls, which were attenuated by rosuvastatin treatment. Glomerulosclerosis and tubulointerstitial fibrosis in DSH rats were attenuated by rosuvastatin treatment. The messenger RNA expression of TNF-alpha, IL-1beta, IFN-gamma, MCP1, ICAM-1 and ET-1 was increased in DSH, which was attenuated by rosuvastatin treatment. The expression of ED-1, TGF-beta and CTGF was increased in the kidney of DSH, which was counteracted by rosuvastatin treatment. CONCLUSION: Rosuvastatin is effective in preventing progression of renal injury in DSH, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects.
BACKGROUND: Pleiotropic effects of statins represent potential mechanisms for the treatment of end organ damage in hypertension. This study has investigated the effects of rosuvastatin (10 mg/kg/day) on renal function impairment, glomerulosclerosis and tubulointerstitial fibrosis in deoxycorticosterone acetate (DOCA)-salthypertensive (DSH) rat. METHODS:Rats were implanted with DOCA strips (200 mg/kg) on 1 week after unilateral nephrectomy. Rats received a controlled diet with or without rosuvastatin. Three weeks after DOCA implantation, systolic blood pressure (SBP) was measured by tail-cuff method. The glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome stain. The tumour necrosis factor (TNF-alpha), interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), monocyte chemoattractant protein1 (MCP1), intercellular adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) were determined by real-time polymerase chain reaction. The expression of ED-1, transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) was determined in the kidney by immunoblotting and immunohistochemistry. RESULTS: In DSH rats, SBP was increased, which was not affected by rosuvastatin treatment. Creatinine clearance was decreased while urinary albumin excretion ratio was increased in DSH rats compared with controls, which were attenuated by rosuvastatin treatment. Glomerulosclerosis and tubulointerstitial fibrosis in DSH rats were attenuated by rosuvastatin treatment. The messenger RNA expression of TNF-alpha, IL-1beta, IFN-gamma, MCP1, ICAM-1 and ET-1 was increased in DSH, which was attenuated by rosuvastatin treatment. The expression of ED-1, TGF-beta and CTGF was increased in the kidney of DSH, which was counteracted by rosuvastatin treatment. CONCLUSION:Rosuvastatin is effective in preventing progression of renal injury in DSH, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects.
Authors: Erica Peres de Barros; Angélica Beatriz Garcia-Pinto; Priscilla Yório Machado; Mário José dos Santos Pereira; Jorge José de Carvalho Journal: J Mol Histol Date: 2011-06-14 Impact factor: 2.611
Authors: Xuexiang Wang; Ashley C Johnson; Jennifer M Sasser; Jan M Williams; Leah C Solberg Woods; Michael R Garrett Journal: Am J Physiol Renal Physiol Date: 2016-03-02
Authors: Eun Hui Bae; In Jin Kim; Ji Hong Song; Hong Sang Choi; Chang Seong Kim; Gwang Hyeon Eom; Inkyeom Kim; Hyunju Cha; Joong Myung Cho; Seong Kwon Ma; Soo Wan Kim Journal: Int J Mol Sci Date: 2019-01-25 Impact factor: 5.923
Authors: Seong Kwon Ma; Joon Seok Choi; Soo Yeon Joo; Ha Yeon Kim; Chang Seong Kim; Eun Hui Bae; Jong Un Lee; Soo Wan Kim Journal: Chonnam Med J Date: 2012-12-21