Protein kinase C activation generates superoxide and contributes to impairment of cerebrovasodilation induced by G protein activation after brain injury

Previous studies have observed that activation of protein kinase C (PKC) contributes to generation of superoxide anion (O-2(-)) after fluid percussion brain injury (M). This study was designed to characterize the effects of FPI on the vascular activity of two activators of a pertussis toxin sensitive G protein, mastoparan and mastoparan-7, and the role of PKC dependent O-2(-) generation in such effects in newborn pigs equipped with a closed cranial window. Mastoparan (10(-8), 10(-6) M) elicited pial artery dilation that was blunted by FPI and partially restored by the PKC inhibitor chelerythrine (10(-7) M) or the O-2(-) free radical scavengers e polyethylene glycol superoxide dismutase and catalase (SODCAT) (9 +/- 1 and 16 +/- 1, sham control; 3 +/- 1 and 5 +/- 1, FPI; and 7 +/- 1 and 11 +/- 1%, FPI SODCAT pretreated). Similar results were observed for mastoparan-7 but the inactive analogue mastoparan-17 had no effect on pial artery diameter. Exposure of the cerebral cortex to a xanthine oxidase O-2(-) generating system blunted mastoparan induced pial artery dilation similar to FPI (10 +/- 1 and 17 +/- 1 vs. 2 +/- 1 and 3 +/- 1%). Pertussis toxin (I mug/ml) exposure blocked mastoparan and mastoparan-7 vasodilation. These data show that pertussis toxin sensitive G protein activation elicits cerebrovasodilation that is blunted following FPI in a PKC dependent manner. These data also show that O-2(-) generation similarly blunts G protein mediated cerebrovasodilation. These data suggest that PKC dependent O-2(-) generation contributes to impaired G protein mediated cerebrovasodilation after FPI. (C) 2003 Elsevier Science B.V. All rights reserved.