Startseite Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats

  • Lakhwinder Singh , Atul Arya EMAIL logo und Sumeet Gupta
Veröffentlicht/Copyright: 19. April 2018

Abstract

Background

Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in reduced nitric oxide level and low expression of endothelial nitric oxide synthase by which nitric oxide level get reduced. In the present study, we examined the role of ANP in reduced nitric oxide level, which may be responsible in controlling diabetic nephropathy in rats.

Methods

Serum nitrite/nitrate ratio, blood urea nitrogen, protein in urine, urinary output, serum creatinine, serum cholesterol, kidney weight, kidney hypertrophy, renal cortical collagen content, thiobarbituric acid level, and antioxidant enzymatic activities were assessed.

Results

Treatment with lisinopril (1 mg/kg) significantly attenuated diabetes-induced elevated glucose level, cholesterol level, and protein in urine concentration. Whereas ANP at low dose (5 μg/kg) has no effect on elevated markers of diabetic nephropathy, treatment with intermediate (10 μg/kg) and high-dose ANP (20 μg/kg) significantly attenuated the diabetes-induced increased blood urea nitrogen, protein in urine, urinary output, creatinine, cholesterol, kidney weight, kidney hypertrophy, renal collagen content, and thiobarbituric acid level and reduced endogenous antioxidant enzymatic activities. High dose of ANP was more effective in attenuating the diabetes-induced nephropathy, renal oxidative stress, and antioxidant enzyme activity as compared with the treatment with low-dose ANP (5 μg/kg), intermediate-dose ANP (10 μg/kg), or lisinopril (1 mg/kg, employed as standard agent). Administration of erythro-9-(2-hydroxy-3-nonyl)adenine, a phosphodiesterase-2 inhibitor (3 mg/kg), in combination with high-dose ANP significantly attenuated high-dose ANP induced ameliorative effects in diabetic nephropathy.

Conclusions

Taken together, these results indicate that diabetes-induced oxidative stress and lipid alterations may be responsible for the induction of nephropathy in diabetic rats. ANP at intermediate and high doses have prevented the development of diabetes-induced nephropathy by reducing the cholesterol level, protein in urine concentration, and renal oxidative stress and by increasing the nitrite/nitrate ratio, certainly providing the direct nephroprotective action.

Acknowledgments

We would like to thank the I. K. Gujral Punjab Technical University Jalandhar (India) for the support and encouragement.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Xue R, Gui D, Zheng L, Zhai R, Wang F, Wang N. Mechanistic insight and management of diabetic nephropathy: recent progress and future perspective. J Diabetes Res 2017;2017:1839809.10.1155/2017/1839809Suche in Google Scholar PubMed

2. Ramachandran A, Das AK, Joshi SR, Yajnik CS, Shah S, Kumar KM. Current status of diabetes in India and need for novel therapeutic agents. J Assoc Physicians India 2010;58:7–9.Suche in Google Scholar

3. Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998;339:321–8.10.1056/NEJM199807303390507Suche in Google Scholar PubMed

4. Anand-Srivastava MB. Natriuretic peptide receptor-C signaling and regulation. Peptides 2005;26:1044–59.10.1016/j.peptides.2004.09.023Suche in Google Scholar PubMed

5. Costa MA, Elesgaray R, Loria A, Balaszczuk AM, Arranz C. Atrial natriuretic peptide influence on nitric oxide system in kidney and heart. Regul Peptides 2004;118:151–7.10.1016/j.regpep.2003.12.009Suche in Google Scholar

6. Oliveira-Souza M, Malnic G, Mello-Aires M. Atrial natriuretic peptide impairs the stimulatory effect of angiotensin II on H+-ATPase. Kidney Int 2002;62:1693–9.10.1046/j.1523-1755.2002.00604.xSuche in Google Scholar PubMed

7. Brismar H, Holtbäck U, Aperia A. Mechanisms by which intrarenal dopamine and ANP interact to regulate sodium metabolism. Clin Exp Hypertens 2000;22:303–7.10.1081/CEH-100100079Suche in Google Scholar PubMed

8. Jujić A, Nilsson PM, Engström G, Hedblad B, Melander O, Magnusson M. Atrial natriuretic peptide and type 2 diabetes development – biomarker and genotype association study. PLoS One 2014;9:e89201.10.1371/journal.pone.0089201Suche in Google Scholar PubMed

9. Reyes AA, Karl IE, Kissane J, Klahr S. l-Arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats. J Am Soc Nephrol 1993;4:1039–45.10.1681/ASN.V441039Suche in Google Scholar PubMed

10. Pieper GM, Siebeneich W, Moore-Hilton G, Roza AM. Reversal by l-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat. Diabetologia 1997;40:910–5.10.1007/s001250050767Suche in Google Scholar PubMed

11. Marzia M, David RT. A pharmacologic analysis of mechanical hyperalgesia in streptozotocin/diabetic rats. Pain 1998;76:151–7.10.1016/S0304-3959(98)00037-2Suche in Google Scholar PubMed

12. Lott JA, Turner K. Evaluation of Trinder’s glucose oxidase method for measuring glucose in serum and urine. Clin Chem 1975;21:1754–60.10.1093/clinchem/21.12.1754Suche in Google Scholar PubMed

13. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470–5.10.1093/clinchem/20.4.470Suche in Google Scholar PubMed

14. Jamall IS, Finelli VN, Que Hee SS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 1981;112:70–5.10.1016/0003-2697(81)90261-XSuche in Google Scholar PubMed

15. Sastry KV, Moudgal RP, Mohan J, Tyagi JS, Rao GS. Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium alloy. Anal Biochem 2002;306:79–82.10.1006/abio.2002.5676Suche in Google Scholar PubMed

16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.10.1016/0003-2697(79)90738-3Suche in Google Scholar PubMed

17. Ellman GL. Tissue sulphydryl groups. Arch Biochem Biophys 1959;82:70–7.10.1016/0003-9861(59)90090-6Suche in Google Scholar

18. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.10.1016/S0021-9258(19)45228-9Suche in Google Scholar

19. Aebi H. Catalase in vitro. Method Enzym 1984;105:121–6.10.1016/S0076-6879(84)05016-3Suche in Google Scholar

20. Ichinose K, Kawasaki E, Eguchi K. Recent advancement of understanding pathogenesis of type-1 diabetes and potential relevance to diabetic nephropathy. Am J Nephrol 2007;27:554.10.1159/000107758Suche in Google Scholar PubMed

21. Vaishya R, Singh J, Lal H. Effect of irbesartan on streptozotocin-induced diabetic nephropathy: an interventionary study. Indian J Clin Biochem 2008;23:195–7.10.1007/s12291-008-0043-1Suche in Google Scholar PubMed PubMed Central

22. Laursen JB, Boesgaard S, Trautner S, Rubin I, Poulsen HE, Aldershvile J. Endothelium-dependent vasorelaxation is inhibited by in-vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase. Free Radic Res 2001;35:387–94.10.1080/10715760100300901Suche in Google Scholar PubMed

23. Ulker S, McKeown P, Bayraktutan U. Vitamins reverse endothelial dysfunction through regulation of eNOS and NADPH oxidase activities. Hypertension 2003;41:534–41.10.1161/01.HYP.0000057421.28533.37Suche in Google Scholar PubMed

24. Murthy KS, Teng B, Jin J, Makhlouf GM. G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor. Am J Physiol 1998;275:C1409.10.1152/ajpcell.1998.275.6.C1409Suche in Google Scholar

25. Elahi ME, Kong YX, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev 2009;2:259–69.10.4161/oxim.2.5.9441Suche in Google Scholar PubMed

26. Clempus RE, Griendling KK. Reactive oxygen species signalling in vascular smooth muscle cells. Cardiovasc Res 2006;71:216–25.10.1016/j.cardiores.2006.02.033Suche in Google Scholar

27. MacFarland RT, Zelus BD, Beavo JA. High concentrations of a cGMP-stimulated phosphodiesterase mediate ANP-induced decreases in cAMP and steroidogenesis in adrenal glomerulosa cells. J Biol Chem 1991;266:136–42.10.1016/S0021-9258(18)52413-3Suche in Google Scholar PubMed

Received: 2017-10-28
Accepted: 2018-03-17
Published Online: 2018-04-19
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Review
  3. Rabbits and men: relating their ages
  4. Minireview
  5. Orphan drugs: trends and issues in drug development
  6. Phytotherapy
  7. Influence of Loranthus micranthus on hepatic and renal antioxidant status and impaired glycolytic flux in streptozotocin-induced diabetic rats
  8. Garlic (Allium sativum) increases SIRT1 and SIRT2 gene expressions in the kidney and liver tissues of STZ- and STZ+niacinamide-induced diabetic rats
  9. Reproduction
  10. A comparative study of the effect of stress on the cognitive parameters in women with increased body mass index before and after menopause
  11. Comparative effect of the aqueous extracts of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis on the sexual maturation of pregnant mare serum gonadotrophin-primed immature female rats
  12. Oxidative Stress
  13. Effect of L-carnitine on the skeletal muscle contractility in simvastatin-induced myopathy in rats
  14. Infection
  15. Anti-plasmodial activity of sodium acetate in Plasmodium berghei-infected mice
  16. Vascular Conditions
  17. Role of atrial natriuretic peptide in controlling diabetic nephropathy in rats
  18. Inflammation
  19. Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic rats treated orally with magnesium
  20. Effects of artemisinin, with or without lumefantrine and amodiaquine on gastric ulcer healing in rat
  21. Behavior and Neuroprotection
  22. Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice
  23. Hematological Profile
  24. Interactive effects of alcohol and chloroquine on hematologic profile of Wistar rats
  25. Metabolism
  26. Effects of α-(prazosin and yohimbine) and β-receptors activity on cAMP generation and UCP1 gene expression in brown adipocytes
  27. Differential sensitivity of chronic high-fat-diet-induced obesity in Sprague-Dawley rats
  28. Cardiovascular-Pulmonary Interactions
  29. A pilot study exploring the impact of cardiac medications on ciliary beat frequency: possible implications for clinical management
  30. Genotoxicity and Cytotoxicity
  31. Effects of a new chlorhexidine varnish on Streptococcus mutans biofilm formation in vitro
Heruntergeladen am 27.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2017-0146/html?lang=de
Button zum nach oben scrollen