Influence of brain injury on vasopressin-induced pial artery vasodilation: Role of superoxide anion

The present study was designed to investigate the effect of fluid percussion brain injury (FPI) on vasopressin-induced pial artery vasodilation and the role of superoxide anion generation in those observed effects. In the piglet, it was observed previously that FPI produces pial artery constriction associated with free radical generation, Anesthetized piglets equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. FPI of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Vasopressin in physiological and pharmacological concentrations (10 and 1,000 mu U/ml) produced vasodilation that was reversed to constriction after FPI (15 +/- 1 vs. -8 +/- 1 and 25 +/- 1 vs. -13 +/- 1% for 10 and 1,000 mu U/ml before and after injury, respectively). Vasopressin-induced dilation was associated with increased cerebrospinal fluid guanosine 3',5'-cyclic monophosphate, and these biochemical changes were blunted by FPI (407 +/- 12 and 720 +/- 28 vs. 268 +/- 4 and 272 +/- 5 fmol/ml for control and 10 mu U/ml before and after injury, respectively). In contrast, polyethylene glycol superoxide dismutase (PEG-SOD) and catalase pretreatment 30 min before FPI partially restored vasopressin-induced pial artery dilation (14 +/- 1 vs. 3 +/- 1 and 22 +/- 1 vs. 2 +/- 4% for 10 and 1,000 mu U/ml before and after FPI, respectively). Similarly, biochemical changes associated with vasopressin dilation were also partially restored by PEG-SOD and catalase after FPI. These data show that vasopressin is reversed from a dilator to a vasoconstrictor after FPI and suggest that superoxide anion generation contributes to the alteration of vasopressin cerebrovascular effects after injury and that such altered vasopressin cerebrovascular effects contribute to pial vasoconstriction after FPI.