TY - JOUR
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
AU - Weisinger, Jose R.
AU - Rodriguez-Iturbe, Bernardo
N1 - Funding Information:
This work was partly supported by funding by a grant from the Fondo Nacional de Ciencia y Tecnologia (FONACIT) grant 2005000283, Venezuela (to B.R.I.), by National Institutes of Health grants DK073183 and HL085793 (to Y.C.L.), and from Clinical Practice Funds (to M.F.).
PY - 2014
Y1 - 2014
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.
KW - cardiac hypertrophy
KW - fibroblast growth factor
KW - paricalcitol.
KW - renin-angiotensin system
KW - uremia
KW - Vitamin D
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U2 - 10.1093/ajh/hpt177
DO - 10.1093/ajh/hpt177
M3 - Article
C2 - 24072555
AN - SCOPUS:84887224544
VL - 27
SP - 720
EP - 726
JO - American Journal of Hypertension
JF - American Journal of Hypertension
SN - 0895-7061
IS - 5
ER -