Therapeutic Effects of Hydralazine on Renal Ischemia-Reperfusion Injury in Rat.

  • Fatemeh Ahmadi Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
  • Saeed Hajihashemi Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
  • Ali Rahbari Department of Pathology, Arak University of Medical Sciences, Arak, Iran.
  • Fatemeh Ghanbari Department of Pharmacology, Islamic Azad University, Arak Branch, Arak, Iran.


Objective: Renal ischemia-reperfusion (I-R) induces acute kidney injury (AKI). In this study, the effect of hydralazine was investigated on the renal injury induced by the I-R in rats.
Methods: AKI was induced with bilateral obstruction of the renal artery and vein for 20 minutes following with 24 hours of reperfusion. Hydralazine (5mg/kg) was injected intraperitoneally as post- treatment.
Results: Hydralazine significantly increased the levels of renal clearance of creatinine and renal blood flow, while was decreasing by I-R. Also, hydralazine significantly improved levels of serum electrolytes (sodium and potassium) that were impaired by I-R. The tissue MDA levels were significantly suppressed by hydralazine.
Conclusion: According to the results, the post treatment of hydralazine had a therapeutic effect on renal ischemia-reperfusion because improved ion reabsorption and excretion and increased renal blood flow and glomerular filtration rate and decreased lipid peroxidation.
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1. Makris K, Spanou L. Acute kidney injury: definition, pathophysiology and clinical phenotypes. The Clinical Biochemist Reviews. 2016;37(2):85.
2. Case J, Khan S, Khalid R, Khan A. Epidemiology of acute kidney injury in the intensive care unit. Critical care research and practice. 2013;2013.
3. Le Clef N, Verhulst A, D’Haese PC, Vervaet BA. Unilateral renal ischemia-reperfusion as a robust model for acute to chronic kidney injury in mice. PloS one. 2016;11(3):e0152153.
4. Padanilam BJ. Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis. American Journal of Physiology-Renal Physiology. 2003;284(4):F608-F27.
5. Salvadori M, Rosso G, Bertoni E. Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. World journal of transplantation. 2015;5(2):52.
6. Xu B, Bobek G, Makris A, Hennessy A. Antihypertensive methyldopa, labetalol, hydralazine, and clonidine reversed tumour necrosis factor‐α inhibited endothelial nitric oxide synthase expression in endothelial‐trophoblast cellular networks. Clinical and Experimental Pharmacology and Physiology. 2017;44(3):421-7.
7. Rocchiccioli JP. Hydralazine in heart failure: a study of the mechanism of action in human blood vessels: University of Glasgow; 2015.
8. Hendrickson MD, Poyton RO. Crosstalk between nitric oxide and hypoxia-inducible factor signaling pathways: an update. Research and Reports in Biochemistry. 2015;5:147-61.
9. Packer M, Meller J, Medina N, Gorlin R, Herman MV. Dose requirements of hydralazine in patients with severe chronic congestive heart failure. The American journal of cardiology. 1980;45(3):655-60.
10. Mikaelian I, Coluccio D, Hirkaler GM, Downing JC, Rasmussen E, Todd J, et al. Assessment of the toxicity of hydralazine in the rat using an ultrasensitive flow-based cardiac troponin I immunoassay. Toxicologic pathology. 2009;37(7):878-81.
11. Hesketh EE, Czopek A, Clay M, Borthwick G, Ferenbach D, Kluth D, et al. Renal ischaemia reperfusion injury: a mouse model of injury and regeneration. Journal of visualized experiments: JoVE. 2014(88).
12. Suleyman Z, Sener E, Kurt N, Comez M, Yapanoglu T. The effect of nimesulide on oxidative damage inflicted by ischemia–reperfusion on the rat renal tissue. Renal failure. 2015;37(2):323-31.
13. Zou L, Wang W, Liu S, Zhao X, Lyv Y, Du C, et al. Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2016;1862(2):182-91.
14. Hajihashemi S, Hamidizad Z, Rahbari A, Ghanbari F, Motealeghi ZA. Effects of cobalamin (Vitamin B12) on gentamicin induced nephrotoxicity in rat. Drug research. 2017;67(12):710-8.
15. Mukai K, Kuda Y, Shibamoto T, Tanida M, Kurata Y, Yokoyama H. Renal response to anaphylaxis in anesthetized rats and isolated perfused rat kidneys: roles of nitric oxide. The Journal of Physiological Sciences. 2018;68(5):689-97.
16. Hajihashemi S, Jafarian T, Ahmadi M, Rahbari A, Ghanbari F. Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin Induced Nephrotoxicity in Rats. Drug research. 2018;68(07):387-94.
17. Cao Y, Gao X, Yang Y, Ye Z, Wang E, Dong Z. Changing expression profiles of long non-coding RNAs, mRNAs and circular RNAs in ethylene glycol-induced kidney calculi rats. BMC genomics. 2018;19(1):660.
18. Antony AS, Gomathy S, Rajmohan T, Anoop P, Issaic C. Pharmacological evaluation of curcumin for its nephroprotective activity in 5/6 nephrectomized rat model. Drug Invention Today. 2018;10(1).
19. Kristensen MLV, Kierulf‐Lassen C, Nielsen PM, Krag S, Birn H, Nejsum LN, et al. Remote ischemic perconditioning attenuates ischemia/reperfusion‐induced downregulation of AQP2 in rat kidney. Physiological reports. 2016;4(13):e12865.
20. Chole RH, Patil RN, Basak A, Palandurkar K, Bhowate R. Estimation of serum malondialdehyde in oral cancer and precancer and its association with healthy individuals, gender, alcohol, and tobacco abuse. Journal of cancer research and therapeutics. 2010;6(4):487.
21. Ustundag Y, Huysal K, Kahvecioglu S, Demirci H, Yavuz S, Sambel M, et al. Establishing reference values and evaluation of an in-house ferric reducing antioxidant power (FRAP) colorimetric assay in microplates. The European Research Journal. 2016;2(2):126.
22. Ahmadi M, Hajihashemi S, Rahbari A, Ghanbari F. The effects of diclofenac on renal toxicity disorders induced by gentamicin in rats. Journal of Babol University of Medical Sciences. 2018;20(2):33-41.
23. Yu C, Qi D, Sun J-F, Li P, Fan H-Y. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities. Scientific reports. 2015;5:11822.
24. Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Comprehensive Physiology. 2011;2(2):1303-53.
25. Chatauret N, Badet L, Barrou B, Hauet T. Ischemia-reperfusion: From cell biology to acute kidney injury. Progrès en urologie. 2014;24:S4-S12.
26. Miller WL, Cavero PG, Aarhus LL, Heublein DM, Burnett Jr JC. Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effects are attenuated by nitroglycerin in vivo. American journal of hypertension. 1993;6(2):156-63.
27. McComb MN, Chao JY, Ng TM. Direct vasodilators and sympatholytic agents. Journal of cardiovascular pharmacology and therapeutics. 2016;21(1):3-19.
28. Krishnan S, Kraehling J, Eitner F, Bénardeau A, Sandner P. The impact of the nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling cascade on kidney health and disease: a preclinical perspective. International journal of molecular sciences. 2018;19(6):1712.
29. Singh RR, Easton LK, Booth LC, Schlaich MP, Head GA, Moritz KM, et al. Renal nitric oxide deficiency and chronic kidney disease in young sheep born with a solitary functioning kidney. Scientific reports. 2016;6:26777.
30. Vallon V. Tubular transport in acute kidney injury: relevance for diagnosis, prognosis and intervention. Nephron. 2016;134(3):160-6.
31. Palmer BF. Potassium homeostasis in chronic kidney disease. Nephrology news & issues. 2016;30(4):suppl 8-10, 2-3.
32. Mount P, Power DA. Nitric oxide in the kidney: functions and regulation of synthesis. Acta physiologica. 2006;187(4):433-46.
33. Li C, Salisbury R, Ely D. Hydralazine reverses stress-induced elevations in blood pressure, angiotensin II, testosterone, and coronary pathology in a social colony model. ISRN Pathology. 2011;2011.
34. Haynes W, Hand M, Dockrell M, Eadington D, Lee M, Hussein Z, et al. Physiological role of nitric oxide in regulation of renal function in humans. American Journal of Physiology-Renal Physiology. 1997;272(3):F364-F71.
35. Sharma S. Nitric oxide and the kidney. Indian J Nephrol. 2004;14(3):77-84.
36. Grover A, Daniels E. Calcium and Contractility: Smooth Muscle: Springer Science & Business Media; 2012.
37. Sabbahy ME, Vaidya VS. Ischemic kidney injury and mechanisms of tissue repair. Wiley Interdisciplinary Reviews: Systems Biology and Medicine. 2011;3(5):606-18.
38. Hutchens MP, Dunlap J, Hurn PD, Jarnberg PO. Renal ischemia: does sex matter? Anesthesia & Analgesia. 2008;107(1):239-49.
39. Cabell KS, Ma L, Johnson P. Effects of antihypertensive drugs on rat tissue antioxidant enzyme activities and lipid peroxidation levels. Biochemical pharmacology. 1997;54(1):133-41.
40. Cheng YW, Chiou GC. Antioxidant effect of hydralazine on retinal pigment epithelial cells and its potential use in the therapy of age-related macular degeneration. International Journal of Ophthalmology. 2008;8(6):1059-64.
41. P Basile D, C Yoder M. Renal endothelial dysfunction in acute kidney ischemia reperfusion injury. Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders). 2014;14(1):3-14.
42. Mercatello A, editor Changes in renal function induced by anesthesia. Annales francaises d'anesthesie et de reanimation; 1990.
43. Elkayam U, Weber L, Campese VM, Massry SG, Rahimtoola SH. Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure. Journal of the American College of Cardiology. 1984;4(6):1261-7.
44. Zeisberg E, Zeisberg M. A rationale for epigenetic repurposing of hydralazine in chronic heart and kidney failure. J Clin Epigenet. 2016;2(1).
45. Elkayam U, Cohen G, Gogia H, Mehra A, Johnson JV, Chandraratna PAN. Renal vasodilatory effect of endothelial stimulation in patients with chronic congestive heart failure. Journal of the American College of Cardiology. 1996;28(1):176-82.
46. Badavi M, Naseri MKG, Pirmoradi L, Hosseini F. Beta Carotene Modulates Nitric Oxide Production in the Renal Ischemia/Reperfusion Injury in Rat. Zahedan Journal of Research in Medical Sciences. 2017;19(3).
47. Zuckerman R, Patel M, Costanzo EJ, Dounis H, Haj RA, Seyedali S, et al. Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis. Brazilian Journal of Nephrology. 2018(AHEAD):0-.
How to Cite
AHMADI, Fatemeh et al. Therapeutic Effects of Hydralazine on Renal Ischemia-Reperfusion Injury in Rat.. Journal of Contemporary Medical Sciences, [S.l.], v. 5, n. 6, dec. 2019. ISSN 2413-0516. Available at: <>. Date accessed: 10 july 2020.