Investigation of the Pathogenesis and Treatment Efficiency of Bevacizumab-Induced Hypertension in the Rat Model


  • Mehmet Ali Balci Assistant in Internal Medicine
  • Musa Özgür Özyiğit Associate Professor in Pathology
  • Volkan İpek Assistant in Pathology
  • İlker Mustafa Kafa Associate Professor in Anatomy
  • Ender Kurt Professor in Medicine



Bevacizumab, hypertension, valsartan, rat model


Bevacizumab is known to reduce Vascular Endothelial Growth Factor (VEGF) to undetectable levels when used in conjunction with chemotherapy. Hypertension is a frequent adverse effect of bevacizumab, although its mechanism(s) remain unclear. In this study, our aim was to examine the pathogenesis of bevacizumab-induced hypertension and to investigate the treatment efficacy of valsartan. A total of 24 Wistar Albino female rats were included in the study. Rats were divided into three groups with 8 rats in each, as follows: The control group, bevacizumab group and bevacizumab + valsartan group. Blood pressure, blood urea nitrogen and serum creatinine levels were measured, urine samples were collected for 24 hours statistical analyses were performed using IBM SPSS 20 software pack. Nephrectomy specimens in bevacizumab and bevacizumab + valsartan groups exhibited varying degrees of renal injury. Although valsartan was able to reduce the bevacizumab-induced rise in blood pressure, it could not prevent the development of nephropathy. Conclusions these findings suggest that hypertension occurring secondary to bevacizumab treatment in rats may be associated with mechanisms involving renal injury.

Author Biographies

Mehmet Ali Balci, Assistant in Internal Medicine

Department of Internal Medicine, Uludag University Medical Faculty

Musa Özgür Özyiğit, Associate Professor in Pathology

Department of Faculty of Veterinary Medicine, Uludag University

Volkan İpek, Assistant in Pathology

Department of Faculty of Veterinary Medicine, Uludag University

İlker Mustafa Kafa, Associate Professor in Anatomy

Department of Anatomy,, Uludag University

Ender Kurt, Professor in Medicine

Department of Oncology, Uludag University Medical Faculty


Bayar MK, Ö. E., Özercan İ, Erhan ÖL. (1998). Tavşanlarda tekrarlanan dozlarda kullanılan sevofluranın oluşturduğu renal histopatolojik değişiklikler ve plazma florür düzeyine etkileri. Anestezi Dergisi, 6, 144.
George, B. A., Zhou, X. J., & Toto, R. (2007). Nephrotic syndrome after bevacizumab: case report and literature review. Am J Kidney Dis, 49(2), e23-29. doi:10.1053/j.ajkd.2006.11.024
Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., . . . Kabbinavar, F. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 350(23), 2335-2342. doi:10.1056/NEJMoa032691
Izzedine, H., Rixe, O., Billemont, B., Baumelou, A., & Deray, G. (2007). Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension. Am J Kidney Dis, 50(2), 203-218. doi:10.1053/j.ajkd.2007.04.025
Johnson, D. H., Fehrenbacher, L., Novotny, W. F., Herbst, R. S., Nemunaitis, J. J., Jablons, D. M., . . . Kabbinavar, F. (2004). Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 22(11), 2184-2191. doi:10.1200/JCO.2004.11.022
Miller, K. D., Chap, L. I., Holmes, F. A., Cobleigh, M. A., Marcom, P. K., Fehrenbacher, L., . . . Rugo, H. S. (2005). Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol, 23(4), 792-799. doi:10.1200/JCO.2005.05.098
Sugimoto, H., Hamano, Y., Charytan, D., Cosgrove, D., Kieran, M., Sudhakar, A., & Kalluri, R. (2003). Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem, 278(15), 12605-12608. doi:10.1074/jbc.C300012200
Syrigos, K. N., Karapanagiotou, E., Boura, P., Manegold, C., & Harrington, K. (2011). Bevacizumab-induced hypertension: pathogenesis and management. BioDrugs, 25(3), 159-169. doi:10.2165/11590180-000000000-00000
Touyz, R. M., Lang, N. N., Herrmann, J., van den Meiracker, A. H., & Danser, A. H. J. (2017). Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition. Hypertension, 70(2), 220-226. doi:10.1161/HYPERTENSIONAHA.117.08856
Zhao, T., Wang, X., Xu, T., Xu, X., & Liu, Z. (2017). Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients: A systematic review and comprehensive meta-analysis. Oncotarget, 8(31), 51492-51506. doi:10.18632/oncotarget.18190




How to Cite

Balci, M. A., Özyiğit, M. Özgür, İpek, V., Kafa, İlker M., & Kurt, E. (2019). Investigation of the Pathogenesis and Treatment Efficiency of Bevacizumab-Induced Hypertension in the Rat Model. Medical Laboratory Technology Journal, 5(1), 16–23.