## 4 Discussion
Interestingly, constricted pre-exercise brachial artery baseline diameter under HPM\({}_{2.5}\) conditions in this study revealed a similar magnitude of vasoconstriction to the previous studies with a high concentration of PM\({}_{2.5}\) exposure (150-200 ug/m\({}^{3}\)) [18; 34]. We speculate that increased sympathetic nerve activity and endothelin-1 (ET-1) secretion, which is an intrinsic vasoconstrticr, constricted the brachial artery in HPM\({}_{2.5}\) conditions. PM\({}_{2.5}\) inhalation was found to rapidly upset the autonomic nervous system balance by activating the sympathetic nervous system [32]. Moreover, elevated systemic and local oxidative stress and inflammation by PM\({}_{2.5}\) inhalation may increase ET-1 production [18; 35]. Delayed pre-exercise TTP was found in HPM\({}_{2.5}\) conditions compared to LPM\({}_{2.5}\) conditions. Delayed peak dilation has been associated with the risks of CVD [36; 37; 38; 39]. Increasedarterial stiffness caused by PM\({}_{2.5}\) exposure possibly induced the slower pre-exercise TTP in the HPM\({}_{2.5}\) visit, although mechanisms of delayed TTP are unclear. In two previous studies, shortened TTP was found to be associated with a decrease in arterial stiffness, which makes it possible to infer the relationship between TTP and arterial stiffness that may increase with exposure to air pollution [40,41]. Additionally, PM\({}_{2.5}\)-induced oxidative stress and inflammation might impair the mechanosensor of endothelium and alter enzyme rates related to vasodilation signaling pathways. Moreover, the pre-exercise SRAUC in HPM\({}_{2.5}\) showed a lower tendency compared to LPM\({}_{2.5}\) conditions (\(p=0.08\)). This might occur due to the impaired vascular shear stress sensors and cause delayed TTP. Furthermore, the diameter change rate in response to reactive hyperemia can be slowed down by increased sympathetic nervous system activation due to PM\({}_{2.5}\) exposure [32]. Therefore, delayed vascular smooth muscle changes in response to hyperemia may occur in HPM\({}_{2.5}\) conditions before the exercise intervention. However, future studies are necessary to explore the potential mechanisms of delayed TTP by PM\({}_{2.5}\). Our study demonstrated the significantly increased brachial artery baseline diameter after exercising in only the HPM\({}_{2.5}\) condition. The different response of baseline diameter to an acute aerobic exercise between HPM\({}_{2.5}\) and LPM\({}_{2.5}\) conditions might be related to a smaller baseline diameter before the exercise intervention in the HPM\({}_{2.5}\) condition than the LPM\({}_{2.5}\) condition. Increased SR during the aerobic exercise may have redeemed the baseline diameter of the brachial artery, although the pre-exercise baseline diameter of the brachial artery can be constricted in the HPM\({}_{2.5}\) visit, as we discussed above. Additionally, aerobic exercise can decrease plasma ET-1 concentration, which attenuates ET-1-induced brachial artery constriction [42]. The increased blood flow in the respiratory system during exercise is also likely to help reduce the circulating ET-1 by binding to ET\({}_{\text{B}}\) receptors in the lungs [43]. Thus, we assume that treadmill running helps to recover the constricted baseline diameter of the brachial artery in the HPM\({}_{2.5}\) condition. The strength of our study was that exercise intervention was performed in naturally formed high and low indoor PM\({}_{2.5}\) conditions with ambient air. Additionally, it provides insight into the response of vascular endothelial function to acute aerobic exercise in HPM\({}_{2.5}\) conditions that we often encounter in real life. Moreover, our results might convey the importance of managing PM\({}_{2.5}\) concentration in indoor exercise facilities. However, several limitations should be mentioned. First, our sample size was small, and we did not analyze physiological mechanisms to explain our new findings.