Paricalcitol downregulates myocardial renin-angiotensin and fibroblast growth factor expression and attenuates cardiac hypertrophy in uremic rats.
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.
['Freundlich|Michael|M|', 'Li|Yan C|YC|', 'Quiroz|Yasmir|Y|', 'Bravo|Yanauri|Y|', 'Seeherunvong|Wacharee|W|', 'Faul|Christian|C|', 'Weisinger|Jose R|JR|', 'Rodriguez-Iturbe|Bernardo|B|']
D000806:Angiotensin-Converting Enzyme Inhibitors D000818:Animals D000959:Antihypertensive Agents D001794:Blood Pressure D006332:Cardiomegaly D004195:Disease Models, Animal D015536:Down-Regulation D004656:Enalapril D004872:Ergocalciferols D005346:Fibroblast Growth Factors D006973:Hypertension D008297:Male D009206:Myocardium D009392:Nephrectomy D012333:RNA, Messenger D017207:Rats, Sprague-Dawley D051496:Receptor, Fibroblast Growth Factor, Type 1 D012084:Renin-Angiotensin System D014511:Uremia
fibroblast growth factor cardiac hypertrophy Vitamin D renin-angiotensin system uremia paricalcitol.