Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Natalya Bodyak, Juan Carlos Ayus, Steven Achinger, Venkatesha Shivalingappa, Qingen Ke, Yee Shiuan Chen, Debra L. Rigor, Isaac Stillman, Hector Tamez, Paul E. Kroeger, Ruth R. Wu-Wong, S. Ananth Karumanchi, Ravi Thadhani, Peter M. Kang

Research output: Contribution to journalArticlepeer-review

299 Scopus citations

Abstract

Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH) 2D2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS+PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS+PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.

Original languageEnglish (US)
Pages (from-to)16810-16815
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number43
DOIs
StatePublished - Oct 23 2007
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • Heart failure
  • Paricalcitol
  • Renal failure

ASJC Scopus subject areas

  • General

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