Document Detail

Heart Remodeling and Ischemia-Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol.
MedLine Citation:
PMID:  24924917     Owner:  NLM     Status:  Publisher    
Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
Emiliano Raúl Diez; Liliana Berta Altamirano; Isabel Mercedes García; Luciana Mazzei; Natalia Jorgelina Prado; Miguel Walter Fornes; Fernando Darío Cuello Carrión; Amira Zulma Ponce Zumino; León Ferder; Walter Manucha
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-12
Journal Detail:
Title:  Journal of cardiovascular pharmacology and therapeutics     Volume:  -     ISSN:  1940-4034     ISO Abbreviation:  J. Cardiovasc. Pharmacol. Ther.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602617     Medline TA:  J Cardiovasc Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© The Author(s) 2014.
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