Prazosin protects myocardial cells against anoxia-reoxygenation injury via the extracellular signal-regulated kinase signaling pathway

Ischemic heart disease (including coronary arterial atherosclerosis, or vascular cavity stenosis or occlusion) remains the leading cause of disease-associated mortality worldwide. Prazosin, a receptor blocker of postsynaptic adrenaline, is essential in expanding peripheral arteries, which decreases peripheral vascular resistance, and regulates anti-hypertensive action. However, the mechanisms underlying the effects of prazosin have not been fully elucidated. The aim of the present study was to investigate the protective effects of prazosin on myocardial cells against anoxia-reoxygenation injury in a mouse model. The regulatory effects of prazosin on blood lipid levels and blood pressure were investigated in experimental mice. Furthermore, inflammation responses and oxidative stress in myocardial cells were analyzed in mice treated with prazosin. Apoptotic myocardial cells were investigated in experimental mice treated with prazosin. In addition, apoptotic gene expression levels were evaluated in myocardial cells. Extracellular signal-regulated kinase (ERK) expression and phosphorylation was investigated in myocardial cells in mice with anoxia-reoxygenation injury following prazosin treatment. The activity and expression levels of nuclear factor of activated T cells (NF-AT), activator protein 1 (AP-1) and necrosis factor (NF)-κB were observed in myocardial cells. Furthermore, histological analyses were performed to investigate the benefits of prazosin treatment on anoxia-reoxygenation injury. The results of the present study identified that prazosin decreased the expression levels of inflammatory factors, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10 and IL-1 in the serum of mice exhibiting hypoxia/reoxygenation injury. Oxidative stress was observed to be improved and the apoptosis rate was decreased in myocardial cells in anoxia-reoxygenation injury model mice treated with prazosin. ERK expression and phosphorylation was upregulated, and expression levels of NF-AT, AP-1 and NF-κB were downregulated in the myocardial cells of mice treated with prazosin. Blood lipid levels and blood pressure of the anoxia-reoxygenation injury model mice were markedly improved following treatment with prazosin. Histological analysis indicated that the area, circumference fragmentation and segmentation of myocardial cells were significantly improved following prazosin treatment. Thus, these results indicate that prazosin treatment decreases inflammation responses, oxidative stress, and apoptosis of myocardial cells via regulation of the ERK signaling pathway. The findings indicate that prazosin may present as a potential therapeutic agent for the treatment of hypoxia/reoxygenation injury.