Suppression of renin-angiotensin gene expression in the kidney by paricalcitol

Michael Freundlich, Yasmir Quiroz, Zhongyi Zhang, Yan Zhang, Yanauri Bravo, Jose R. Weisinger, Yan Chun Li, Bernardo Rodriguez-Iturbe

Research output: Contribution to journalArticle

205 Scopus citations

Abstract

The renal renin-angiotensin system plays a major role in determining the rate of chronic renal disease progression. Treatment with activators of the vitamin D receptor retards the progression of experimental chronic renal disease, and vitamin D is known to suppress the renin-angiotensin system in other organs. Here we determined if the beneficial effects of paricalcitol (19-nor 1,25-dihydroxyvitamin D2) were associated with suppression of renin-angiotensin gene expression in the kidney. Rats with the remnant kidney model of chronic renal failure (5/6 nephrectomy) were given two different doses of paricalcitol thrice weekly for 8 weeks. Paricalcitol was found to decrease angiotensinogen, renin, renin receptor, and vascular endothelial growth factor mRNA levels in the remnant kidney by 30-50 percent compared to untreated animals. Similarly, the protein expression of renin, renin receptor, the angiotensin type 1 receptor, and vascular endothelial growth factor were all significantly decreased. Glomerular and tubulointerstitial damage, hypertension, proteinuria, and the deterioration of renal function resulting from renal ablation were all similarly and significantly improved with both treatment doses. These studies suggest that the beneficial effects of vitamin D receptor activators in experimental chronic renal failure are due, at least in part, to down-regulation of the renal renin-angiotensin system.

Original languageEnglish (US)
Pages (from-to)1394-1402
Number of pages9
JournalKidney international
Volume74
Issue number11
DOIs
StatePublished - Dec 1 2008

    Fingerprint

Keywords

  • Paricalcitol
  • Progression
  • Renal insufficiency
  • Renin-angiotensin system
  • Vitamin D
  • Vitamin D receptor activators

ASJC Scopus subject areas

  • Nephrology

Cite this

Freundlich, M., Quiroz, Y., Zhang, Z., Zhang, Y., Bravo, Y., Weisinger, J. R., Li, Y. C., & Rodriguez-Iturbe, B. (2008). Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. Kidney international, 74(11), 1394-1402. https://doi.org/10.1038/ki.2008.408