The Influence of Telmisartan on the Expression of BMP-7 in Rat Kidneys Induced by 8% NaCl
Article Sidebar
Main Article Content
Abstract
Excessive salt intake is one of the factors of high blood pressure leading to kidney disease while telmisartan is one of the antihypertensive drugs used in therapy. Telmisartan not only blocks the angiotensin receptor, which leads to a reduction in blood pressure, but also activates the peroxisome proliferator-activated receptor gamma (PPAR-γ), inhibits the expression of transforming growth factor beta-1 (TGFβ-1) and increases bone morphogenetic protein-7 (BMP-7). This experiment examines whether telmisartan increases the expression of BMP-7 in excess NaCl-induced Wistar rats. For this study, 25 male Wistars aged 2.5 to 3 months and rats weighing 100 to 150 g were used.They were grouped into 5, each consists of 5 rats. Group I (G I) as the first negative control received neither NaCl nor telmisartan. G II as the second negative control received NaCl but no telmisartan. G III, IV and V received NaCl and telmisartan 3, 6 and 12 mg/kg body weight. Treatments were given every day for 8 weeks.On day 56, all rats were sacrificed by neck dislocation and operated on to remove the kidney. BMP-7 expression was measured by immunohistochemical technique. Data were expressed as mean ± standard error. They were analyzed by parametric (ANOVA) or nonparametric (Kruskal-Wallis) testing. A value of p ≤ 0.05 was considered statistically significant. The results showed that the expression of the intraglomerular and extraglomerular protein BMP-7 was higher in the telmisartan-treated group of Wistar rats than in the negative control group (pand<0.05). In summary, intraglomerular and extraglomerular BMP-7 protein expression was higher in male Wistar rats treated with telmisartan and induced with 8% sodium chloride than in negative control group members.
Article Details
References
Blaustein MP, Leenen, FHH, Chen L, Golovina, VA, Hamlyn JM, et al. (2012) How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension. Am J Physiol Heart Circ Physiol 302: H1031–H1049.
Bramlage CP, Tampe B, Koziolek M, Maatouk I, Bevanda J, et al. (2010) Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis. BMC Nephrol 11: 31.
Chambers S (2008) Telmisartan an effective antihypertensive for 24-hour blood pressure control. Drugs in Context 4: 1-14.
Cox N, Pilling D, Gomer RH (2012) NaCl potentiates human fibrocyte differentitaion. Plos One 7: 1-9.
Fatchiyah Arumingtyas EL, Widyarti, S, Rahayu S (2011) Biologi Molekuler "Prinsip Dasar Analisis". Erlangga, Jakarta.
Funao K, Matsuyama M, Kawahito Y, Sano H, Chargui J, et al. (2009) Telmisartan as a peroxisome proliferator-activated receptor- Á ligand is a new target in the treatment of human renal cell carcinoma. Mol Med Rep 2: 193-198.
Goebel M, Clemenz M, Unger T (2006) effective treatment of hypertension by AT1 receptor antagonism: the past and future of telmisartan. Expert Rev Cardiovasc Нer 4: 615-629.
Gould SE, Day M, Jones SS, Doai H (2002) BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. Kidney Int 61: 51-60.
Jawi IM, Yasa IWPS, Suprapta DN, Mahendra AN (2012) Antihypertensive effect and eNOS expressions in NaCl-induced hypertensive rats treated with purple sweet potato. Univ J Med Dent 1: 102-107.
Jöhren O, Dendorfer A, Dominiak P (2004) Cardiovascular and renal function of angiotensin II type-2 receptors. Cardiovasc Res 62: 460-467.
Leenen FH (2010) Нe central role of the brain aldosterone –“ouabain” pathway in salt-sensitive hypertension. BBA-Mol Basis Dis 1802: 1132-1139.
Lync MJ, Raphael SS, Mellor LD, Spare PD, Inwood MJH (1969) Medical Laboratory Technology and Clinical Pathology. W.B. Saunders Company, USA.
Mezzano SA, Ruiz-Ortega M, Egido J (2001) Angiotensin II and renal fibrosis. Hypertension 38: 635-638.
Rotman N, Wahli W (2010) PPAR modulation of kinase-linked receptor signaling in physiology and disease. Physiology (Bethesda) 25: 176-185.
Starr C, McMillan B (2012) Human Biology (9th edn.). Brooks/Cole Cengage Learning, Canada.
Weiskirchen R, Meurer SK, Gressner OA, Herrmann J, Borkhamkamphorst E, et al. (2009) BMP-7 as antagonist of organ fibrosis. Front Biosci 14: 4992-5012.
World Health Organisation (2010) Global Status Report on Noncommunicable Diseases. WHO, Geneva, Switzerland.
Xu L, Liu Y (2013) Administration of telmisartan reduced systolic blood pressure and oxidative stress probably through the activation of pi3k/akt/ enos pathway and no release in spontaneously hypertensive rats. Physiol Res 62: 351-359.
Younis F, Stern N, Limor R, Oron Y, Zangen S, et al. (2010) Telmisartan ameliorates hyperglycemia and metabolic profile in nonobese cohenrosenthal diabetic hypertensive rats via peroxisome proliferator activator receptor–γ activation. Metabolism 59: 1200-1209.
Yu HC, Burrell LM, Black MJ, Wu LL, Dilley RJ, et al. (1998) Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats. Circulation 98: 2621-2628.
Zeisberg M (2006) Bone morphogenic protein-7 and the kidney: Current concepts and open questions. Nephrol Dial Transplant 21: 568-573.
Zeisberg M, Muller GA, Kalluri R (2004) Are there endogenous molecules that protect kidneys from injury? Нe case for bone morphogenic protein-7 (BMP-7). Nephrol Dial Transplant 19: 759-761.
Zhang Y, Shao L, Ma A, Guan G, Wang J, et al. (2014) Telmisartan delays myocardial fibrosis in rats with hypertensive leі ventricular hypertrophy by TGF- b1/Smad signal pathway. Hypertens Res 37: 43-49.
Zhong L, Wang X, Wang S, Yang L, Gao H, et al. (2013) Нe anti-fibroctic effect of bone morphogenic protein-7 (BMP-7) on liver fibrosis. Int J Med Sci 10: 441-450.