Objective:To determine the effects of a pressor agent (phenylephrine and L-arginine) on the abnormal cerebral hemodynamics and on neurologic outcome after a severe cortical impact injury in rats.Design:Prospective, randomized study.Setting:University laboratory.Subjects:Male Long-Evans rats, weighing 300 to 400 g, fasted overnight.Interventions:The animals were anesthetized with isoflurane, and a severe cortical impact injury (velocity, 5 m/sec; deformation, 3 mm) was produced in the right parietal cortex. Five minutes after impact injury, one of the following three treatments were infused: 1 mL saline intravenously for 10 mins, 300 mg/kg L-arginine in 1 mL saline intravenously for 10 mins, or 0.3 μg/kg/min phenylephrine intravenously for 3 hrs. Mean arterial pressure, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser Doppler flow (LDF) at the impact site and in the contralateral parietal cortex were monitored for 3 hrs after the impact injury. Histologic examination of the brain was performed at 2 wks after injury in a separate group of L-arginine- and saline-treated animals.Measurements and Main Results:The immediate response to the impact injury was an increase in ICP, and a decrease in mean arterial pressure, CPP, and LDF. In the saline-treated animals, LDF decreased to <25% of the baseline values at the impact site and stayed at that level for the entire 3-hr monitoring period. On the contralateral side, LDF decreased initially and recovered gradually to approximately 50% of the preimpact baseline value. Infusion of both phenylephrine and L-arginine increased LDF back to near-baseline levels. However, phenylephrine increased ICP significantly, whereas ICP with L-arginine did not change. L-arginine treatment reduced the contusion volume from a median value of 5.28 mm3to 0.63 mm3.Conclusions:Phenylephrine increased cerebral blood flow (CBF) by increasing CPP. L-arginine, however, increased CBF without changing CPP. The improvement in CBF was accompanied by a decrease in neurologic injury. Although the pressor agents are used currently to increase CBF after traumatic brain injury, other strategies may also increase CBF without the potential adverse effects of induced hypertension.