Suppression of renin-angiotensin gene expression in the kidney by paricalcitol.
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 D(2)) 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.
Freundlich
Michael
M
Division of Pediatric Nephrology, Department of Pediatrics, University of Miami, Miami, Florida 33101, USA. mfmefex@pol.net
Quiroz
Yasmir
Y
Zhang
Zhongyi
Z
Zhang
Yan
Y
Bravo
Yanauri
Y
Weisinger
Jose R
JR
Li
Yan Chun
YC
Rodriguez-Iturbe
Bernardo
B
D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004872:Ergocalciferols / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007676:Kidney Failure, Chronic; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000819:agonists*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics
D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol