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Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats.
- Source :
-
The American journal of pathology [Am J Pathol] 2010 Aug; Vol. 177 (2), pp. 622-31. Date of Electronic Publication: 2010 Jul 08. - Publication Year :
- 2010
-
Abstract
- Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent antihypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase.
- Subjects :
- Aged
Animals
Antihypertensive Agents therapeutic use
Humans
Hypertrophy, Left Ventricular pathology
Losartan therapeutic use
Male
Microarray Analysis
Middle Aged
Random Allocation
Rats
Renin blood
Vitamins therapeutic use
Ergocalciferols therapeutic use
Hypertrophy, Left Ventricular drug therapy
Rats, Inbred SHR
Vitamin D analogs & derivatives
Vitamin D therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 177
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 20616348
- Full Text :
- https://doi.org/10.2353/ajpath.2010.091292