During acute sympathetic stress, the overactivation of β-
adrenergic receptors (β-ARs) causes cardiac
fibrosis by triggering
inflammation and
cytokine expression. It is unknown whether exercise training inhibits acute β-AR overactivation-induced
cytokine expression and cardiac injury. Here, we report that running exercise inhibited cardiac
fibrosis and improved cardiac function in mice treated with
isoproterenol (ISO), a β-AR agonist. A
cytokine antibody array revealed that running exercise prevented most of the changes in
cytokine expression induced by ISO. Specifically, ISO-induced upregulation of 18
cytokines was prevented by running exercise. A Kyoto encyclopedia of genes and genomes analysis of these
cytokines revealed that Hedgehog and RAP1 signaling pathways were involved in the regulation of
cytokine expression by exercise. The changes in the expression of some
cytokines that were prevented by exercise were verified by an
enzyme-linked
immunosorbent assay and real-time PCR. In conclusion, running exercise prevented the
cytokine expression changes after acute β-AR overactivation and therefore attenuated cardiac
fibrosis. Acute sympathetic stress is an important risk factor for the patients with
cardiovascular diseases, and the present study revealed that exercise training can prevent against the upregulation of
cytokines and the subsequent cardiac injury induced by acute sympathetic stress, suggesting that exercise training may be beneficial for cardiovascular patients who are in risk of acute sympathetic stress. This finding provides a theoretical basis for the application of exercise training in patients who may suffer from acute sympathetic stress.