The Effect of Nebivolol on Acute Renal Injury Developed After Myocardial Ischemia: A Preclinical Study
PDF
Cite
Share
Request
Original Article
P: 228-234
September 2018

The Effect of Nebivolol on Acute Renal Injury Developed After Myocardial Ischemia: A Preclinical Study

Med Bull Haseki 2018;56(3):228-234
1. Sağlık Bilimleri Üniversitesi Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, İstanbul, Türkiye
2. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Pataloji Anabilim Dalı, İstanbul, Türkiye
3. İstanbul Medipol Üniversitesi Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, İstanbul, Türkiye
4. İstanbul Üniversitesi İstanbul Tıp Fakültesi, Kardiyoloji Anabilim Dalı, İstanbul, Türkiye
No information available.
No information available
Received Date: 18.04.2018
Accepted Date: 06.08.2018
Publish Date: 20.09.2018
PDF
Cite
Share
Request

ABSTRACT

Aim:

During reperfusion of myocardial ischemia, damage can also be seen in the kidneys. Although many studies have been conducted on the underlying mechanisms, the basic mechanism of this interaction is still unknown. We think that this is oxidative/nitrosative damage caused by hypoperfusion. Nebivolol is a beta-blocker with nitric oxide (NO)-mediated effects. In this study, we aimed to investigate the NO-mediated effect of nebivolol on acute renal injury (ARI) developed after myocardial ischemia-reperfusion (IR).

Methods:

Adult male Sprague-Dawley rats were divided into three groups: sham-control, IR-control, and IR-nebivolol. Nebivolol (0.1 mg/kg, intravenous) was administered within the 10 min of reperfusion. IR was performed by surgically anterior descending artery ligation. NO-mediated effects of nebivolol were assessed by hemodynamic, biologic and histologic studies.

Results:

Compared to the sham-control, changes in renal function were not statistically significant in the IR-control (p>0.05). Focal tubular damage findings were also observed in histologic sections. Decrease in superoxide dismutase (SOD) levels together with increase in nitrogen dioxide (NOx)/peroxynitrite (ONOO-) were also significant (p<0.05). On the contrary, consistent with focal tubular regeneration, elevated renal SOD levels together with reduced NOx/ONOO- levels were detected in IR-nebivolol (p<0.05).

Conclusion:

NO-mediated beneficial effects of nebivolol on ARI developing after myocardial IR were shown. The mechanism can be explained by the prevention of nitrosative damage and the protection of NO bioavailability.

References

1
Ronco C, Cruz DN, Ronco F. Cardiorenal syndromes. Curr Opin Crit Care 2009;15:384-91.
2
Frederix I, Dendale P, Schmid JP. Who needs secondary prevention? Eur J Prev Cardiol 2017;24:8-13.
3
Bongartz LG, Braam B, Verhaar MC, et al. Transient nitric oxide reduction induces permanent cardiac systolic dysfunction and worsens kidney damage in rats with chronic kidney disease. Am J Physiol Regul Integr Comp Physiol 2010;298:815-23.
4
Fischer D, Rossa S, Landmesser U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2004;26:65-9.
5
Ortiz PA, Garvin JL. Interaction of O(2)(-) and NO in the thick ascending limb. Hypertension 2002;39:591-96.
6
Wu L, Mayeux PR. Effects of the inducible nitric-oxide synthase inhibitor L-N(6)-(1-iminoethyl)-lysine on microcirculation and reactive nitrogen species generation in the kidney following lipopolysaccharide administration in mice. J Pharmacol Exp Ther 2007;320:1061-7.
7
Wu L, Tiwari MM, Messer KJ, et al. Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice. Am J Physiol Renal Physiol 2007;292:261-8.
8
Rajapakse NW, Nanayakkara S, Kaye DM. Pathogenesis and treatment of the cardiorenal syndrome: Implications of L-arginine-nitric oxide pathway impairment. Pharmacol Ther 2015;154:1-12.
9
Majid DS, Navar LG. Nitric oxide in the control of renal hemodynamics and excretory function. Am J Hypertens 2001;14:74-82.
10
Lee J, Bae EH, Ma SK, Kim SW. Altered nitric oxide system in cardiovascular and renal diseases. Chonnam Med J 2016;52:81-90.
11
Virzì GM, Clementi A, de Cal M, et al. Oxidative stress: dual pathway induction in cardiorenal syndrome type 1 pathogenesis. Oxid Med Cell Longev 2015;2015:391790.
12
Singh RR, Easton LK, Booth LC, et al. Renal nitric oxide deficiency and chronic kidney disease in young sheep born with a solitary functioning kidney. Sci Rep 2016;26:26777.
13
Mercanoğlu GO, Pamukçu B, Safran N, et al. Nebivolol prevents remodeling in a rat myocardial infarction model: an echocardiographic study. Anadolu Kardiyol Derg 2010;10:18-27.
14
Fraccarollo D, Hu K, Galuppo P, Gaudron P, Ertl G. Chronic endothelin receptor blockade attenuates progressive ventricular dilation and improves cardiac function in rats with myocardial infarction: possible involvement of myocardial endothelin system in ventricular remodeling. Circulation 1997;96:3963-73.
15
Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 1985;57:84-95.
16
Chatterjee PK, Cuzzocrea S, Brown PA, et al. Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int 2000;58:658-73.
17
Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.
18
Ohno K, Kuno A, Murase H, et al. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats. Am J Physiol Heart Circ Physiol 2017;313:1130-42.
19
Haase M, Kellum JA, Ronco C. Subclinical AKI--an emerging syndrome with important consequences. Nat Rev Nephrol 2012;8:735-9.
20
Rosner MH, Ronco C, Okusa MD. The role of inflammation in the cardio-renal syndrome: a focus on cytokines and inflammatory mediators. Semin Nephrol 2012;32:70-8.
21
Yu L, Gengaro PE, Niederberger M, Burke TJ, Schrier RW. Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury. Proc Natl Acad Sci U S A 1994;91:1691-5.
22
Cho E, Kim M, Ko YS, et al. Role of inflammation in the pathogenesis of cardiorenal syndrome in a rat myocardial infarction model. Nephrol Dial Transplant 2013;28:2766-78.
23
Cruz DN. Cardiorenal syndrome in critical care: the acute cardiorenal and renocardiac syndromes. Adv Chronic Kidney Dis 2013;20:56-66.
24
Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol 2012; 60:1031-42.
25
Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997;82:291-5.
26
Rubattu S, Mennuni S, Testa M. Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress? Int J Mol Sci 2013;14:23011-32.
27
Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 2011;21:103-15.
28
Nazıroğlu M, Yoldaş N, Uzgur EN, Kayan M. Role of contrast media on oxidative stress, Ca(2+) signaling and apoptosis in kidney. J Membr Biol 2013;246:91-100.
29
Maack C, Böhm M. Targeting mitochondrial oxidative stress in heart failure throttling the afterburner. J Am Coll Cardiol 2011;58:83-6.
30
Lin Y, Bai L, Chen W, Xu S. The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert Opin Ther Targets 2010;14:45-55.
31
Sung CC, Hsu YC, Chen CC, Lin YF, Wu CC. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease. Oxid Med Cell Longev 2013;2013:301982.
32
Gabbai FB, Blantz RC. Role of nitric oxide in renal hemodynamics. Semin Nephrol 1999;19:242-50.
33
Fischer E, Schnermann J, Briggs JP, et al. Ontogeny of NO synthase and renin in juxtaglomerular apparatus of rat kidneys. Am J Physiol 1995;268:1164-76.
34
De Nicola L, Blantz RC, Gabbai FB. Nitric oxide and angiotensin II. Glomerular and tubular interaction in the rat. J Clin Invest 1992;89:1248-56.
35
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 1990;87:1620-24.
36
Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 1991;266:4244-50.
37
Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 1991;288:481-7.
38
Walker LM, Walker PD, Imam SZ, Ali SF, Mayeux PR. Evidence for peroxynitrite formation in renal ischemia-reperfusion injury: studies with the inducible nitric oxide synthase inhibitor L-N(6)-(1-Iminoethyl)lysine. J Pharmacol Exp Ther 2000;295:417-22.
39
Chatterjee PK, Patel NS, Kvale EO, et al. Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury. Kidney Int 2002;61:862-71.
40
Noiri E, Nakao A, Uchida K, et al. Oxidative and nitrosative stress in acute renal ischemia. Am J Physiol Renal Physiol 2001;281:948-57.
41
Pasini AF, Garbin U, Stranieri C, et al. Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients. Am J Hypertens 2008;21:1251-7.
42
Mercanoglu G, Safran N, Gungor M, et al. The effects of nebivolol on apoptosis in a rat infarct model. Circ J 2008;72:660-70.