Dronedarone Administration Prevents Body Weight Gain and Increases Tolerance of the Heart to Ischemic Stress: A Possible Involvement of Thyroid Hormone Receptor α1
| العنوان: | Dronedarone Administration Prevents Body Weight Gain and Increases Tolerance of the Heart to Ischemic Stress: A Possible Involvement of Thyroid Hormone Receptor α1 |
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| المؤلفون: | Panagiotis Moraitis, Iordanis Mourouzis, Dennis V. Cokkinos, Dennis Varonos, Ioannis Paizis, Constantinos Pantos, Konstantinos Sfakianoudis, Stylianos Tzeis, Vassiliki Malliopoulou |
| المصدر: | Thyroid. 15:16-23 |
| بيانات النشر: | Mary Ann Liebert Inc, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, Thyroid Hormones, medicine.medical_specialty, SERCA, Endocrinology, Diabetes and Metabolism, Myocardial Ischemia, Amiodarone, Myocardial Reperfusion Injury, Calcium-Transporting ATPases, In Vitro Techniques, Myosins, Weight Gain, Contractility, Eating, Endocrinology, Hypothyroidism, Isomerism, Heart Rate, Internal medicine, Animals, Medicine, Rats, Wistar, Thyroid hormone binding, Dronedarone, Cardioprotection, Triiodothyronine, Thyroid hormone receptor, L-Lactate Dehydrogenase, business.industry, Myocardium, Heart, Adaptation, Physiological, Myocardial Contraction, Rats, Sarcoplasmic Reticulum, Propylthiouracil, business, Glycogen, Thyroid Hormone Receptors alpha, medicine.drug |
| الوصف: | Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses. |
| تدمد: | 1557-9077 1050-7256 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5045d0a8a56708512f4774669d2feb67Test https://doi.org/10.1089/thy.2005.15.16Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....5045d0a8a56708512f4774669d2feb67 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15579077 10507256 |
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