Cisplatin-induced nephrotoxicity alters blood pressure response to angiotensin II administration in rats

Authors

1 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan; Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran

2 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan; Department of Physiology, Isfahan University of Medical Sciences, Isfahan; IsfahanMN Institute of Basic and Applied Sciences Research, Isfahan, Iran

Abstract

Background: Cisplatin (CP) is an effective chemotherapeutic drug used in the clinic, which is accompanied with nephrotoxicity. CP may also disturb hemodynamics of the circulation system. We have tested the role of CP in mean arterial pressure (MAP) response to graded angiotensin (Ang) II infusion in rats.
Materials and Methods: Male and female rats were treated with CP (2.5 mg/kg/day) for a period of 1-week and compared with the vehicle-treated animals. The blood pressure response to Ang II (100–1000 ng/kg/min) was determined under the anesthesia condition. Endothelial permeability of aorta was measured according to the Evans blue uptake. The kidney tissue was also subjected to histological investigation.




Results: Significant increase in serum levels of blood urea nitrogen and creatinine and pathological findings in CP-treated rats verified CP-induced nephrotoxicity. Significant difference in percentage of change in MAP response to Ang II between male and female rats was detected in vehicle-treated groups (P < 0.05) while in CP-treated animals this response difference was not observed. The groups were not significantly different with regard to the endothelial permeability of aorta while the serum level of nitrite in male rats increased significantly following administration of CP (P < 0.05).
Conclusion: It seems the different response in percentage of change of MAP to graded Ang II infusion between male and female indicates the effect of CP on renin Ang system parameters.

Keywords

1.
Schrier RW. Cancer therapy and renal injury. J Clin Invest 2002;110:743-5.  Back to cited text no. 1
    
2.
Arany I, Sa firstein RL, Cisplatin nephrotoxicity. Semin Nephrol 2003;23:460-464.  Back to cited text no. 2
    
3.
Sueishi K, Mishima K, Makino K, Itoh Y, Tsuruya K, Hirakata H, et al. Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats. Eur J Pharmacol 2002;451:203-8.  Back to cited text no. 3
    
4.
Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002;89:3A-9.  Back to cited text no. 4
    
5.
Levy BI. The potential role of angiotensin II in the vasculature. J Hum Hypertens 1998;12:283-7.  Back to cited text no. 5
    
6.
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG. Angiotensin receptors: Signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol Heart Circ Physiol 2001;281:H2337-65.  Back to cited text no. 6
    
7.
You D, Loufrani L, Baron C, Levy BI, Widdop RE, Henrion D. High blood pressure reduction reverses angiotensin II type 2 receptor-mediated vasoconstriction into vasodilation in spontaneously hypertensive rats. Circulation 2005;111:1006-11.  Back to cited text no. 7
    
8.
Silbiger SR, Neugarten J. The role of gender in the progression of renal disease. Adv Ren Replace Ther 2003;10:3-14.  Back to cited text no. 8
    
9.
Ahmed SB, Kang AK, Burns KD, Kennedy CR, Lai V, Cattran DC, et al. Effects of oral contraceptive use on the renal and systemic vascular response to angiotensin II infusion. J Am Soc Nephrol 2004;15:780-6.  Back to cited text no. 9
    
10.
Chidambaram M, Duncan JA, Lai VS, Cattran DC, Floras JS, Scholey JW, et al. Variation in the renin angiotensin system throughout the normal menstrual cycle. J Am Soc Nephrol 2002;13:446-52.  Back to cited text no. 10
    
11.
Sampson AK, Moritz KM, Jones ES, Flower RL, Widdop RE, Denton KM. Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats. Hypertension 2008;52:666-71.  Back to cited text no. 11
    
12.
Tatchum-Talom R, Eyster KM, Martin DS. Sexual dimorphism in angiotensin II-induced hypertension and vascular alterations. Can J Physiol Pharmacol 2005;83:413-22.  Back to cited text no. 12
    
13.
Xue B, Pamidimukkala J, Hay M. Sex differences in the development of angiotensin II-induced hypertension in conscious mice. Am J Physiol Heart Circ Physiol 2005;288:H2177-84.  Back to cited text no. 13
    
14.
Hutchison FN, Perez EA, Gandara DR, Lawrence HJ, Kaysen GA. Renal salt wasting in patients treated with cisplatin. Ann Intern Med 1988;108:21-5.  Back to cited text no. 14
    
15.
Deegan PM, Nolan C, Ryan MP, Basinger MA, Jones MM, Hande KR. The role of the renin-angiotensin system in cisplatin nephrotoxicity. Ren Fail 1995;17:665-74.  Back to cited text no. 15
    
16.
Saleh S, Ain-Shoka AA, El-Demerdash E, Khalef MM. Protective effects of the angiotensin II receptor blocker losartan on cisplatin-induced kidney injury. Chemotherapy 2009;55:399-406.  Back to cited text no. 16
    
17.
Haghighi M, Nematbakhsh M, Talebi A, Nasri H, Ashrafi F, Roshanaei K, et al. The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: Gender-related differences. Ren Fail 2012;34:1046-51.  Back to cited text no. 17
    
18.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel) 2010;2:2490-518.  Back to cited text no. 18
    
19.
Nematbakhsh M, Ashrafi F, Nasri H, Talebi A, Pezeshki Z, Eshraghi F, et al. A model for prediction of cisplatin induced nephrotoxicity by kidney weight in experimental rats. J Res Med Sci 2013;18:370-3.  Back to cited text no. 19
[PUBMED]  Medknow Journal  
20.
Pezeshki Z, Nematbakhsh M, Nasri H, Talebi A, Pilehvarian AA, Safari T, et al. Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model. Toxicol Int 2013;20:43-7.  Back to cited text no. 20
[PUBMED]  Medknow Journal  
21.
Chen Y, Brott D, Luo W, Gangl E, Kamendi H, Barthlow H, et al. Assessment of cisplatin-induced kidney injury using an integrated rodent platform. Toxicol Appl Pharmacol 2013;268:352-61.  Back to cited text no. 21
    
22.
Gonçalves AR, Fujihara CK, Mattar AL, Malheiros DM, Noronha Ide L, de Nucci G, et al. Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: Strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory. Am J Physiol Renal Physiol 2004;286:F945-54.  Back to cited text no. 22
    
23.
Gandhi SK, Gainer J, King D, Brown NJ. Gender affects renal vasoconstrictor response to Ang I and Ang II. Hypertension 1998;31:90-6.  Back to cited text no. 23
    
24.
Nuver J, De Haas EC, Van Zweeden M, Gietema JA, Meijer C. Vascular damage in testicular cancer patients: A study on endothelial activation by bleomycin and cisplatin in vitro. Oncol Rep 2010;23:247-53.  Back to cited text no. 24
    
25.
Sekijima T, Tanabe A, Maruoka R, Fujishiro N, Yu S, Fujiwara S, et al. Impact of platinum-based chemotherapy on the progression of atherosclerosis. Climacteric 2011;14:31-40.  Back to cited text no. 25
    
26.
Ekor M, Emerole GO, Farombi EO. Phenolic extract of soybean (Glycine max) attenuates cisplatin-induced nephrotoxicity in rats. Food Chem Toxicol 2010;48:1005-12.  Back to cited text no. 26