The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Altered Regulation of Renal Nitric Oxide and Atrial Natriuretic Peptide Systems in Lipopolysaccharide-induced Kidney Injury

  • Bae, Eun-Hui (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Kim, In-Jin (Department of Physiology, Chonnam National University Medical School) ;
  • Ma, Seong-Kwon (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Lee, Jong-Un (Department of Physiology, Chonnam National University Medical School) ;
  • Kim, Soo-Wan (Department of Internal Medicine, Chonnam National University Medical School)
  • Received : 2011.08.09
  • Accepted : 2011.10.06
  • Published : 2010.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

Keywords

References

  1. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, Ognibene FP. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. 1990;113:227-242. https://doi.org/10.7326/0003-4819-113-3-227
  2. Rackow EC, Astiz ME. Pathophysiology and treatment of septic shock. JAMA. 1991;266:548-554. https://doi.org/10.1001/jama.1991.03470040112032
  3. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol. 1997;15:323-350. https://doi.org/10.1146/annurev.immunol.15.1.323
  4. Thiemermann C. Nitric oxide and septic shock. Gen Pharmacol. 1997;29:159-166. https://doi.org/10.1016/S0306-3623(96)00410-7
  5. Carnio EC, Stabile AM, Batalhao ME, Silva JS, Antunes- Rodrigues J, Branco LG, Magder S. Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase. Pflugers Arch. 2005;450:390-394. https://doi.org/10.1007/s00424-005-1400-z
  6. Knowles RG, Moncada S. Nitric oxide as a signal in blood vessels. Trends Biochem Sci. 1992;17:399-402. https://doi.org/10.1016/0968-0004(92)90008-W
  7. Scicluna JK, Mansart A, Ross JJ, Reilly CS, Brown NJ, Brookes ZL. Lipopolysaccharide alters vasodilation to atrial natriuretic peptide via nitric oxide and endothelin-1: time-dependent effects. Eur J Pharmacol. 2009;621:67-70. https://doi.org/10.1016/j.ejphar.2009.08.029
  8. De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981;28:89-94. https://doi.org/10.1016/0024-3205(81)90370-2
  9. Totsune K, Takahashi K, Murakami O, Satoh F, Sone M, Saito T, Sasano H, Mouri T, Abe K. Natriuretic peptides in the human kidney. Hypertension. 1994;24:758-762 https://doi.org/10.1161/01.HYP.24.6.758
  10. Winquist RJ , Faison EP, Waldman SA, Schwartz K, Murad F, Rapoport RM. Atrial natriuretic factor elicits an endothelium- independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci USA. 1984;81:7661-7664. https://doi.org/10.1073/pnas.81.23.7661
  11. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402-408. https://doi.org/10.1006/meth.2001.1262
  12. Chinkers M, Garbers DL. The protein kinase domain of the ANP receptor is required for signaling. Science. 1989;245:1392-1394. https://doi.org/10.1126/science.2571188
  13. Zhang C, Walker LM, Mayeux PR. Role of nitric oxide in lipopolysaccharide-induced oxidant stress in the rat kidney. Biochem Pharmacol. 2000;59:203-209. https://doi.org/10.1016/S0006-2952(99)00324-X
  14. Wang W, Jittikanont S, Falk SA, Li P, Feng L, Gengaro PE, Poole BD, Bowler RP, Day BJ, Crapo JD, Schrier RW. Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure. Am J Physiol Renal Physiol. 2003;284:F532-537. https://doi.org/10.1152/ajprenal.00323.2002
  15. Bachmann S, Bosse HM, Mundel P. Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney. Am J Physiol. 1995;268:F885-898.
  16. Markewitz BA, Michael JR, Kohan DE. Cytokine-induced expression of a nitric oxide synthase in rat renal tubule cells. J Clin Invest. 1993;91:2138-2143. https://doi.org/10.1172/JCI116439
  17. Titheradge MA. Nitric oxide in septic shock. Biochim Biophys Acta. 1999;1411:437-455
  18. Del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang X, Feuerstein GZ. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol. 2000;10:95-112.
  19. Noiri E, Peresleni T, Miller F, Goligorsky MS. In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest. 1996;97:2377-2383. https://doi.org/10.1172/JCI118681
  20. Aiura K, Ueda M, Endo M, Kitajima M. Circulating concentrations and physiologic role of atrial natriuretic peptide during endotoxic shock in the rat. Crit Care Med. 1995;23: 1898-1906. https://doi.org/10.1097/00003246-199511000-00017
  21. Wilkins MR, Redondo J, Brown LA. The natriuretic-peptide family. Lancet. 1997;349:1307-1310. https://doi.org/10.1016/S0140-6736(96)07424-7
  22. Parkes DG, Coghlan JP, McDougall JG, Scoggins BA. Longterm hemodynamic actions of atrial natriuretic factor (99-126) in conscious sheep. Am J Physiol. 1988;254:H811-815.
  23. Roubert P, Lonchampt MO, Chabrier PE, Plas P, Goulin J, Braquet P. Down-regulation of atrial natriuretic factor receptors and correlation with cGMP stimulation in rat cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 1987;148:61-67. https://doi.org/10.1016/0006-291X(87)91076-X

Cited by

  1. Nitric oxide—Important messenger in human body vol.2, pp.3, 2011, https://doi.org/10.4236/ojmip.2012.23014
  2. Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO vol.12, pp.1, 2011, https://doi.org/10.1038/s41467-021-22933-3