Paricalcitol downregulates myocardial renin-angiotensin and fibroblast growth factor expression and attenuates cardiac hypertrophy in uremic rats

Michael Freundlich, Yan C. Li, Yasmir Quiroz, Yanauri Bravo, Wacharee Seeherunvong, Christian H Faul, Jose R. Weisinger, Bernardo Rodriguez-Iturbe

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

BACKGROUND Vitamin D attenuates uremic cardiac hypertrophy, possibly by suppressing the myocardial renin-angiotensin system (RAS) and fibroblast growth factors (FGFs). We compared the suppression of cardiac hypertrophy and myocardial expression of RAS and FGF receptor genes offered by the vitamin D analog paricalcitol (Pc) or the angiotensin-converting enzyme inhibitor enalapril (E) in experimental uremia. METHODS Rats with 5/6 nephrectomy received Pc or E for 8 weeks. Renal function, systolic blood pressure, and cardiac hypertrophy were evaluated. Myocardial expression of RAS genes, brain natriuretic peptide (BNP), and FGF receptor-1 (FGFR-1) were determined using quantitative reverse-transcription (pRT)-PCR. RESULTS Blood pressure, proteinuria, and serum creatinine were significantly higher in untreated uremic animals. Hypertension was significantly reduced by E but only modestly by Pc; however, cardiac hypertrophy in the untreated group was similarly attenuated by Pc or E. Upregulation of myocardial expressions of renin, angiotensinogen, FGFR-1, and BNP in untreated uremic animals was reduced similarly by Pc and E, while the angiotensin II type 1 receptor was downregulated only by E. CONCLUSIONS Uremic cardiac hypertrophy is associated with activation of the myocardial RAS and the FGFR-1. Downregulation of these genes induced by Pc and E RESULTS in similar amelioration of left ventricular hypertrophy despite the different antihypertensive effects of these drugs.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalAmerican Journal of Hypertension
Volume27
Issue number5
DOIs
StatePublished - Jan 1 2014

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Fibroblast Growth Factors
Angiotensins
Cardiomegaly
Renin
Down-Regulation
Renin-Angiotensin System
Fibroblast Growth Factor Receptors
Fibroblast Growth Factor 1
Brain Natriuretic Peptide
Blood Pressure
Vitamin D
Receptor, Fibroblast Growth Factor, Type 1
Genes
Angiotensinogen
Angiotensin Type 1 Receptor
Enalapril
Uremia
Left Ventricular Hypertrophy
Nephrectomy
Proteinuria

Keywords

  • cardiac hypertrophy
  • fibroblast growth factor
  • paricalcitol.
  • renin-angiotensin system
  • uremia
  • Vitamin D

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Paricalcitol downregulates myocardial renin-angiotensin and fibroblast growth factor expression and attenuates cardiac hypertrophy in uremic rats. / Freundlich, Michael; Li, Yan C.; Quiroz, Yasmir; Bravo, Yanauri; Seeherunvong, Wacharee; Faul, Christian H; Weisinger, Jose R.; Rodriguez-Iturbe, Bernardo.

In: American Journal of Hypertension, Vol. 27, No. 5, 01.01.2014, p. 720-726.

Research output: Contribution to journalArticle

Freundlich, Michael ; Li, Yan C. ; Quiroz, Yasmir ; Bravo, Yanauri ; Seeherunvong, Wacharee ; Faul, Christian H ; Weisinger, Jose R. ; Rodriguez-Iturbe, Bernardo. / Paricalcitol downregulates myocardial renin-angiotensin and fibroblast growth factor expression and attenuates cardiac hypertrophy in uremic rats. In: American Journal of Hypertension. 2014 ; Vol. 27, No. 5. pp. 720-726.
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T1 - Paricalcitol downregulates myocardial renin-angiotensin and fibroblast growth factor expression and attenuates cardiac hypertrophy in uremic rats

AU - Freundlich, Michael

AU - Li, Yan C.

AU - Quiroz, Yasmir

AU - Bravo, Yanauri

AU - Seeherunvong, Wacharee

AU - Faul, Christian H

AU - Weisinger, Jose R.

AU - Rodriguez-Iturbe, Bernardo

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N2 - BACKGROUND Vitamin D attenuates uremic cardiac hypertrophy, possibly by suppressing the myocardial renin-angiotensin system (RAS) and fibroblast growth factors (FGFs). We compared the suppression of cardiac hypertrophy and myocardial expression of RAS and FGF receptor genes offered by the vitamin D analog paricalcitol (Pc) or the angiotensin-converting enzyme inhibitor enalapril (E) in experimental uremia. METHODS Rats with 5/6 nephrectomy received Pc or E for 8 weeks. Renal function, systolic blood pressure, and cardiac hypertrophy were evaluated. Myocardial expression of RAS genes, brain natriuretic peptide (BNP), and FGF receptor-1 (FGFR-1) were determined using quantitative reverse-transcription (pRT)-PCR. RESULTS Blood pressure, proteinuria, and serum creatinine were significantly higher in untreated uremic animals. Hypertension was significantly reduced by E but only modestly by Pc; however, cardiac hypertrophy in the untreated group was similarly attenuated by Pc or E. Upregulation of myocardial expressions of renin, angiotensinogen, FGFR-1, and BNP in untreated uremic animals was reduced similarly by Pc and E, while the angiotensin II type 1 receptor was downregulated only by E. CONCLUSIONS Uremic cardiac hypertrophy is associated with activation of the myocardial RAS and the FGFR-1. Downregulation of these genes induced by Pc and E RESULTS in similar amelioration of left ventricular hypertrophy despite the different antihypertensive effects of these drugs.

AB - BACKGROUND Vitamin D attenuates uremic cardiac hypertrophy, possibly by suppressing the myocardial renin-angiotensin system (RAS) and fibroblast growth factors (FGFs). We compared the suppression of cardiac hypertrophy and myocardial expression of RAS and FGF receptor genes offered by the vitamin D analog paricalcitol (Pc) or the angiotensin-converting enzyme inhibitor enalapril (E) in experimental uremia. METHODS Rats with 5/6 nephrectomy received Pc or E for 8 weeks. Renal function, systolic blood pressure, and cardiac hypertrophy were evaluated. Myocardial expression of RAS genes, brain natriuretic peptide (BNP), and FGF receptor-1 (FGFR-1) were determined using quantitative reverse-transcription (pRT)-PCR. RESULTS Blood pressure, proteinuria, and serum creatinine were significantly higher in untreated uremic animals. Hypertension was significantly reduced by E but only modestly by Pc; however, cardiac hypertrophy in the untreated group was similarly attenuated by Pc or E. Upregulation of myocardial expressions of renin, angiotensinogen, FGFR-1, and BNP in untreated uremic animals was reduced similarly by Pc and E, while the angiotensin II type 1 receptor was downregulated only by E. CONCLUSIONS Uremic cardiac hypertrophy is associated with activation of the myocardial RAS and the FGFR-1. Downregulation of these genes induced by Pc and E RESULTS in similar amelioration of left ventricular hypertrophy despite the different antihypertensive effects of these drugs.

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