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

Academic Article

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. © 2013 American Journal of Hypertension, Ltd.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 7016812
  • Author List

  • Freundlich M; Li YC; Quiroz Y; Bravo Y; Seeherunvong W; Faul C; Weisinger JR; Rodriguez-Iturbe B
  • Start Page

  • 720
  • End Page

  • 726
  • Volume

  • 27
  • Issue

  • 5