Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats

Juan Kong, Gene H. Kim, Minjie Wei, Tao Sun, George Li, Shu Q. Liu, Xinmin Li, Ishir Bhan, Qun Zhao, Ravi Thadhani*, Yan Chun Li

*Corresponding author for this work

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)622-631
Number of pages10
JournalAmerican Journal of Pathology
Volume177
Issue number2
DOIs
StatePublished - Aug 2010

    Fingerprint

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kong, J., Kim, G. H., Wei, M., Sun, T., Li, G., Liu, S. Q., Li, X., Bhan, I., Zhao, Q., Thadhani, R., & Li, Y. C. (2010). Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats. American Journal of Pathology, 177(2), 622-631. https://doi.org/10.2353/ajpath.2010.091292