Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
| Autor: | Natalia Jorgelina Prado, Fernando Darío Cuello Carrión, Liliana Altamirano, Miguel W. Fornés, Emiliano Raúl Diez, Luciana Mazzei, Isabel Mercedes García, Walter Manucha, León Ferder, Amira Ponce Zumino |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Paricalcitol
Farmacología y Farmacia medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD Receptor expression Ischemia Action Potentials Myocardial Reperfusion Injury Arrhythmias Rats Inbred WKY Calcitriol receptor Receptor Angiotensin Type 1 Coronary Circulation Internal medicine medicine Vitamin D and neurology Animals Pharmacology (medical) Ventricular remodeling Pharmacology Ventricular Remodeling business.industry Myocardium Arrhythmias Cardiac medicine.disease Angiotensin II Rats Medicina Básica Endocrinology Reperfusion Injury Ergocalciferols Receptors Calcitriol Female Vitamin D Receptor Cardiology and Cardiovascular Medicine business Reperfusion injury Ureteral Obstruction medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology and Therapeutics. 20:211-220 |
| ISSN: | 1940-4034 1074-2484 |
| DOI: | 10.1177/1074248414538704 |
| Popis: | 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. Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Altamirano, Liliana Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Ponce Zumino, Amira Zulma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Ferder, León. Universidad de Puerto Rico; Puerto Rico Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|