Modulating effects of preconditioning exercise in the expression of ET-1 and BNP via HIF-1α in ischemically injured brain

It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.