title: Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial vitamin d receptors deficiency in obstructive nephropathy are reversed by paricalcitol.
abstract: 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.
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina diez.emiliano@fcm.uncu.edu.ar.
authors.forename: Emiliano Raúl
authors.initials: ER
authors.lastname: Diez
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina Pathology Department, Medical Sciences College, National University of Cuyo, Mendoza, Argentina.
authors.forename: Liliana Berta
authors.initials: LB
authors.lastname: Altamirano
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Isabel Mercedes
authors.initials: IM
authors.lastname: García
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Mazzei
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Natalia Jorgelina
authors.initials: NJ
authors.lastname: Prado
authors.affiliation: Institute of Histology and Embryology of Mendoza, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Miguel Walter
authors.initials: MW
authors.lastname: Fornes
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Fernando Darío Cuello
authors.initials: FD
authors.lastname: Carrión
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina.
authors.forename: Amira Zulma Ponce
authors.initials: AZ
authors.lastname: Zumino
authors.affiliation: Department of Physiology and Pharmacology, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.
authors.forename: León
authors.initials: L
authors.lastname: Ferder
authors.affiliation: Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina Pathology Department, Medical Sciences College, National University of Cuyo, Mendoza, Argentina.
authors.forename: Walter
authors.initials: W
authors.lastname: Manucha
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003326:Coronary Circulation; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis; D018167:Receptors, Calcitriol / Q000032:analysis / Q000172:deficiency*; D014517:Ureteral Obstruction / Q000150:complications* / Q000378:metabolism
chemical_list: D004872:Ergocalciferols; D044140:Receptor, Angiotensin, Type 1; D018167:Receptors, Calcitriol; C084656:paricalcitol
keywords: arrhythmias; paricalcitol; reperfusion injury; ureteral obstruction; ventricular remodeling; vitamin D receptor