1. Role of dopamine D2 receptors in ischemia/reperfusion induced apoptosis of cultured neonatal rat cardiomyocytes
- Author
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Guangdong Yang, Rui Wang, Lina Wang, Shuzhi Bai, Changqing Xu, Guang-Wei Li, Hongzhu Li, Yan Lin, Jin Guo, Hong Li, Jun Gao, Hong-Xia Li, Yajun Zhao, Chun-ming Jiang, Weihua Zhang, Li-ping Han, Baofeng Yang, Lingyun Wu, and Ye Tian
- Subjects
Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Myocardial Ischemia ,Ischemia ,lcsh:Medicine ,Apoptosis ,Myocardial Reperfusion Injury ,Fas ligand ,Internal medicine ,Dopamine receptor D2 ,medicine ,Animals ,Myocytes, Cardiac ,Pharmacology (medical) ,Rats, Wistar ,Receptor ,Molecular Biology ,Bromocriptine ,Cells, Cultured ,Biochemistry, medical ,Receptors, Dopamine D2 ,Chemistry ,Research ,lcsh:R ,Biochemistry (medical) ,Cell Biology ,General Medicine ,medicine.disease ,Rats ,Dopamine D2 Receptor Antagonists ,Endocrinology ,Animals, Newborn ,Haloperidol ,Calcium ,Reperfusion injury ,medicine.drug - Abstract
Background Myocardial ischemia/reperfusion injury is the major cause of morbidity and mortality for cardiovascular diseases. Dopamine D2 receptors are expressed in cardiac tissues. However, the roles of dopamine D2 receptors in myocardial ischemia/reperfusion injury and cardiomyocyte apoptosis are unclear. Here we investigated the effects of both dopamine D2 receptors agonist (bromocriptine) and antagonist (haloperidol) on apoptosis of cultured neonatal rat ventricular myocytes induced by ischemia/reperfusion injury. Methods Myocardial ischemia/reperfusion injury was simulated by incubating primarily cultured neonatal rat cardiomyocytes in ischemic (hypoxic) buffer solution for 2 h. Thereafter, these cells were incubated for 24 h in normal culture medium. Results Treatment of the cardiomyocytes with 10 μM bromocriptine significantly decreased lactate dehydrogenase activity, increased superoxide dismutase activity, and decreased malondialdehyde content in the culture medium. Bromocriptine significantly inhibited the release of cytochrome c, accumulation of [Ca2+]i, and apoptosis induced by ischemia/reperfusion injury. Bromocriptine also down-regulated the expression of caspase-3 and -9, Fas and Fas ligand, and up-regulated Bcl-2 expression. In contrast, haloperidol (10 μM) had no significant effects on the apoptosis of cultured cardiomyocytes under the aforementioned conditions. Conclusions These data suggest that activation of dopamine D2 receptors can inhibit apoptosis of cardiomyocytes encountered during ischemia/reperfusion damage through various pathways.
- Published
- 2011