The Korean Journal of Physiology and Pharmacology

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

DOI QR Code

Changes in Endothelin Receptor Type B and Neuronal Nitric Oxide Synthase in Puromycin Aminonucleoside-Induced Nephrotic Syndrome

  • Bae, Eun-Hui (Department of Internal Medicine, Chonnam National University Medical School) ;
  • Kim, Soo-Wan (Department of Internal Medicine, Chonnam National University Medical School)
  • Received : 2010.07.01
  • Accepted : 2010.08.06
  • Published : 2010.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B ($ET_BR$) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of $ET_BR$ increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal $ET_BR$ synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

Keywords

References

  1. Vande Walle JG, Donckerwolcke RA. Pathogenesis of edema formation in the nephrotic syndrome. Pediatr Nephrol. 2001;16: 283-293. https://doi.org/10.1007/s004670000512
  2. Deschenes G, Doucet A. Collecting duct Na,K-ATPase activity correlates with urinary sodium excretion in rat nephrotic syndrome. J Am Soc Nephrol. 2000;11:604-615.
  3. Kim SW, Schou UK, Peters CD, de Seigneuxs S, Kwon TH, Knepper MA, Jonassen TE, Frokiaer J, Nielsen S. Increased apical targeting of renal epithelial sodium channel subunits and decreased expression of type 2 11beta-hydroxysteroid dehydrogenase in rats with CCl4-induced decompensated liver cirrhosis. J Am Soc Nephrol. 2005;16:3196-3210. https://doi.org/10.1681/ASN.2004080721
  4. Kim SW, Wang W, Sassen MC, Choi KC, Han JS, Knepper MA, Jonassen TE, Frokiaer J, Nielsen S. Biphasic changes of epithelial sodium channel abundance and trafficking in common bile duct ligation-induced liver cirrhosis. Kidney Int. 2006;69: 89-98. https://doi.org/10.1038/sj.ki.5000018
  5. Marsen TA, Schramek H, Dunn MJ. Renal actions of endothelin: Linking cellular signaling pathways to kidney disease. Kidney Int. 1994;45:336-344. https://doi.org/10.1038/ki.1994.43
  6. Tsukahara H, Ende H, Magazine HI, Bahou WF, Goligorsky MS. Molecular and functional characterization of the nonisopeptide- selective ETB receptor in endothelial cells. Receptor coupling to nitric oxide synthase. J Biol Chem. 1994;269:21778- 21785.
  7. Kohan DE. Endothelins in the normal and diseased kidney. Am J Kidney Dis. 1997;29:2-26. https://doi.org/10.1016/S0272-6386(97)90004-4
  8. Abassi Z, Gurbanov K, Rubinstein I, Better OS, Hoffman A, Winaver J. Regulation of intrarenal blood flow in experimental heart failure: role of endothelin and nitric oxide. Am J Physiol. 1998;274:F766-F774.
  9. Zou AP, Cowley AW Jr. Nitric oxide in renal cortex and medulla. An in vivo microdialysis study. Hypertension. 1997;29:194-198. https://doi.org/10.1161/01.HYP.29.1.194
  10. Romero JC, Lahera V, Salom MG, Biondi ML. Role of the endothelium-dependent relaxing factor nitric oxide on renal function. J Am Soc Nephrol. 1992;2:1371-1387.
  11. Bugaj V, Pochynyuk O, Mironova E, Vandewalle A, Medina JL, Stockand JD. Regulation of the epithelial $Na^{+}$ channel by endothelin-1 in rat collecting duct. Am J Physiol Renal Physiol. 2008;295:F1063-F10670. https://doi.org/10.1152/ajprenal.90321.2008
  12. 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
  13. Stoos BA, Carretero OA, Farhy RD, Scicli G, Garvin JL. Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells. J Clin Invest. 1992;89:761-765. https://doi.org/10.1172/JCI115653
  14. Plato CF, Garvin JL. Nitric oxide, endothelin and nephron transport: potential interactions. Clin Exp Pharmacol Physiol. 1999;26:262-268. https://doi.org/10.1046/j.1440-1681.1999.03028.x
  15. Plato CF, Pollock DM, Garvin JL. Endothelin inhibits thick ascending limb chloride flux via ET(B) receptor-mediated NO release. Am J Physiol Renal Physiol. 2000;279:F326-F333. https://doi.org/10.1152/ajprenal.2000.279.2.F326
  16. Pollock DM, Pollock JS. Evidence for endothelin involvement in the response to high salt. Am J Physiol Renal Physiol. 2001; 281:F144-F150. https://doi.org/10.1152/ajprenal.2001.281.1.F144
  17. Hoffman A, Abassi ZA, Brodsky S, Ramadan R, Winaver J. Mechanisms of big endothelin-1-induced diuresis and natriuresis: role of ET(B) receptors. Hypertension. 2000;35:732-739. https://doi.org/10.1161/01.HYP.35.3.732
  18. Stricklett PK, Hughes AK, Kohan DE. Endothelin-1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways. Am J Physiol Renal Physiol. 2006;290:F1315-F1319. https://doi.org/10.1152/ajprenal.00450.2005
  19. Nakano D, Pollock JS, Pollock DM. Renal medullary ETB receptors produce diuresis and natriuresis via NOS1. Am J Physiol Renal Physiol. 2008;294:F1205-F1211. https://doi.org/10.1152/ajprenal.00578.2007
  20. Kohan DE. The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. Curr Opin Nephrol Hypertens. 2006;15:34-40. https://doi.org/10.1097/01.mnh.0000186852.15889.1a
  21. Ge Y, Bagnall A, Stricklett PK, Strait K, Webb DJ, Kotelevtsev Y, Kohan DE. Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol. 2006;291:F1274-F1280. https://doi.org/10.1152/ajprenal.00190.2006
  22. Nakano D, Pollock DM. Contribution of endothelin a receptors in endothelin 1-dependent natriuresis in female rats. Hypertension. 2009;53:324-330. https://doi.org/10.1161/HYPERTENSIONAHA.108.123687