The pathophysiology and mechanism of primary blast-induced traumatic brain injury (bTBI) have not yet been elucidated. We previously observed the occurrence of spreading depolarization (SD) and transient hyperemia/hyperoxemia followed by persistent oligemia/hypoxemia in the cortex of the rat brain exposed to a laserinduced shock wave (LISW). However, the mechanism of such hemodynamic abnormalities is not clear. In this study, we investigated the involvement of nitric oxide (NO), which is known as an endothelium-derived relaxing factor (EDRF) and also as a substance associated with vasoconstriction. By the inhibition of NO synthesis, we found that the transient hyperemia/hyperoxemia immediately after LISW application was diminished and the level of persistent oligemia/hypoxemia was mitigated even when SD occurred. The results suggest that hemodynamic abnormalities caused by an LISW in the rat cortex was associated with an increased NO production and its vasodilatory/vasoconstrictory effects.