Abstract
Objective Nicorandil has been widely used for the treatment of angina pectoris and myocardial infarction. The purpose of this study was to investigate whether nicorandil plays a protective role in exhaustive exercise (EE)-induced myocardial injury. Methods Here, we applied the rat EE model and treated them with exercise preconditioning (EP, reported to protect the heart) or different doses of nicorandil gavage, respectively, to explore whether there are protective effects of single EP or nicorandil or a combination of both and the potential mechanism. Forty-nine male Sprague Dawley rats were randomly divided into control, EE, EP + EE, nicorandil (with low, middle, and high dose) + EE, and EP + nicorandil (middle dose) + EE. Blood samples and myocardial tissues were collected to analyze the myocardial injury-related index. Results EE induced myocardial structural damage and altered the myocardial injury markers, which were partially reversed by pretreatment of nicorandil. In addition, oxidative stress and inflammation lead to the accumulation of reactive oxygen species (ROS) products and further damage to the myocardium, while pretreatment of nicorandil reduces the oxidative stress response and inflammation. Moreover, nicorandil suppressed the myocardial apoptosis induced by EE, as indicated by a decrease of Bax and caspase-3 expression and an increase of Bcl-2 expression. Finally, the pathway in which nicorandil plays a role may be involved in the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Pretreatment of nicorandil increased the protein level of myocardial eNOS and NO production. Conclusion Our result demonstrated that nicorandil has protective effects in EE-induced myocardial injury with dose-dependent effects. A combination of nicorandil and EP can further improve the protective effects. Taken together, nicorandil can be potentially used as an intervention method in EE-induced myocardial injury.
Highlights
Numerous research studies have well documented the benefits of exercise, such as improved maximal oxygen consumption, weight loss, skeletal muscle function, myocardial health, and so on
We demonstrated that pretreatment of different doses of nicorandil gavage or exercise preconditioning (EP) or a combination of both can protect EE hearts from acute EE-induced myocardial injury. is protection may be related to the reactive oxygen species (ROS) scavengers (SOD) and endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway
Our results showed that EE stimulation significantly lowered the protective antioxidant enzyme Superoxide dismutase (SOD) activity and increased the MDA level in the heart, while pretreatment of high-dose nicorandil or middledose nicorandil plus EP significantly increased SOD activity, and all nicorandil groups and the EP group significantly decreased the level of MDA. ese results indicate that the protective effects of nicorandil in the EE model may be related to the physiological processes of antioxidative stress effects
Summary
Numerous research studies have well documented the benefits of exercise, such as improved maximal oxygen consumption, weight loss, skeletal muscle function, myocardial health, and so on. Recent studies have well documented the protective effects of exercise preconditioning (EP) in EE and ischemia/reperfusion (I/R) injury by activating the pathways abovementioned [5], which initiate absolute or relative recurrent transient myocardial ischemia, and this is similar to the ischemic preconditioning (IP) process [6,7,8]. Nicorandil, which is an adenosine triphosphate-sensitive potassium (KATP) channel activator and a donor for NO and can serve valid benefits to acute myocardial infarction (AMI) [9, 10] in basic and clinical research, has not been investigated during acute EE-induced myocardial injury. Clinical research has shown that the cardioprotective effects of nicorandil are similar to the effects of IP in ischemic injury and myocardial infarction patients [10]
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