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 Citations (Scopus)

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

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Angiotensins
Renin
Kidney
Gene Expression
Renin-Angiotensin System
Calcitriol Receptors
Chronic Renal Insufficiency
Chronic Kidney Failure
Angiotensinogen
Angiotensin Type 1 Receptor
Vascular Endothelial Growth Factor Receptor
paricalcitol
Nephrectomy
Proteinuria
Vitamin D
Vascular Endothelial Growth Factor A
Disease Progression
Down-Regulation
Hypertension
Messenger RNA

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., ... 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

Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. / Freundlich, Michael; Quiroz, Yasmir; Zhang, Zhongyi; Zhang, Yan; Bravo, Yanauri; Weisinger, Jose R.; Li, Yan Chun; Rodriguez-Iturbe, Bernardo.

In: Kidney International, Vol. 74, No. 11, 01.12.2008, p. 1394-1402.

Research output: Contribution to journalArticle

Freundlich, M, Quiroz, Y, Zhang, Z, Zhang, Y, Bravo, Y, Weisinger, JR, Li, YC & Rodriguez-Iturbe, B 2008, 'Suppression of renin-angiotensin gene expression in the kidney by paricalcitol', Kidney International, vol. 74, no. 11, pp. 1394-1402. https://doi.org/10.1038/ki.2008.408
Freundlich, Michael ; Quiroz, Yasmir ; Zhang, Zhongyi ; Zhang, Yan ; Bravo, Yanauri ; Weisinger, Jose R. ; Li, Yan Chun ; Rodriguez-Iturbe, Bernardo. / Suppression of renin-angiotensin gene expression in the kidney by paricalcitol. In: Kidney International. 2008 ; Vol. 74, No. 11. pp. 1394-1402.
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