Role of endothelial nitric oxide synthase in exercise preconditioning-induced improvement of myocardial ischemia-reperfusion injury

doi:10.12307/2023.993

Abstract

Abstract: BACKGROUND: Exercise is an effective strategy to prevent and treat various cardiovascular diseases and protect the heart from ischemia-reperfusion injury. Its mechanism of action needs to be studied in depth.
OBJECTIVE: To observe the effect of aerobic exercise preconditioning on myocardial ischemia-reperfusion injury and to explore the effect of endothelial nitric oxide synthase (eNOS) activation (including coupling and phosphorylation).
METHODS: Eighty adult Wistar rats were randomly divided into sedentary (n=40) and exercise (n=40) groups. The rats in the exercise group were subjected to aerobic exercise for 8 weeks while those in the sedentary group were quietly fed and caged. After 8 weeks of intervention, three experiments were performed. (1) Experiment 1: After the last training, cardiac function, cardiac nitric oxide metabolite content and cardiac eNOS, phosphorylated enOS-S1177, eNOS dimer and eNOS monomer protein expression levels were detected. (2) Experiment 2: Rats were divided into sedentary control group, exercise control group, sedentary+eNOS inhibitor group, exercise+eNOS inhibitor group, all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment. eNOS inhibitor was continuously infused into the sedentary+eNOS inhibitor group and exercise+eNOS inhibitor group 10 minutes before reperfusion, and cardiac function and myocardial infarction area were detected 3 hours after reperfusion. (3) Experiment 3: Rats were divided into sedentary control group, exercise control group, sedentary+eNOS coupler group and exercise+eNOS coupler group, all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment. The rats in the sedentary+eNOS coupler group and exercise+eNOS coupler group were treated with eNOS coupler. Myocardial infarct area, cardiac nitric oxide metabolite content, cardiac protein expression of eNOS, phosphorylated enos-S1177, eNOS dimer, eNOS monomer and 3-nitrotyrosine were detected 3 hours after reperfusion. The phosphorylated eNOS-S1177/eNOS ratio reflected the phosphorylated/dephosphorylated level of eNOS and eNOS dimer/monomer ratio reflected eNOS coupling/uncoupling level.
RESULTS AND CONCLUSION: Experiment 1: Compared with the sedentary group, the exercise group had increased cardiac output and left ventricular ejection fraction (P < 0.05), increased nitrite and S-nitrosothiol contents (P < 0.05), upregulated phosphorylated eNOS-S1177, eNOS protein expression and phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), eNOS dimer protein expression and eNOS dimer/monomer ratios were elevated (P < 0.05). Experiment 2: Compared with the sedentary control group, left ventricular development pressure increased (P < 0.05) and myocardial infarct area decreased (P < 0.05) in the exercise control group. Compared with the exercise control group, left ventricular development pressure decreased (P < 0.05) and myocardial infarct area increased (P < 0.05) in the exercise+eNOS inhibitor group. Experiment 3: Compared with the sedentary control group, the exercise control group had increased left ventricular developmental pressure (P < 0.05), decreased myocardial infarct area (P < 0.05), decreased phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), decreased eNOS dimer/monomer ratio (P < 0.05), increased S-nitrosothiol content (P < 0.05), and decreased 3-nitrotyrosine protein expression (P < 0.05). Compared with the exercise control group, the exercise+eNOS coupler group had decreased left ventricular developmental pressure (P < 0.05), increased myocardial infarct area (P < 0.05), increased phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), increased eNOS dimer/monomer ratio (P < 0.05), and elevated 3-nitro tyrosine protein expression (P < 0.05). To conclude, aerobic exercise preconditioning could induce cardioprotection, which is related to uncoupling and dephosphorylation of eNOS during cardiac ischemia-reperfusion, thereby inhibiting the excessive production of nitric oxide and reducing nitro-oxidative stress.

Key words: exercise preconditioning, endothelial nitric oxide synthase, phosphorylation/dephosphorylation, coupling/uncoupling, ischemia-reperfusion injury, nitro-oxidative stress

CLC Number:

Lou Guo, Zhang Yan, Fu Changxi. Role of endothelial nitric oxide synthase in exercise preconditioning-induced improvement of myocardial ischemia-reperfusion injury[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(8): 1283-1288.

Figures/Tables 3

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