Role of Vasopressin in Altered Pial Artery Responses to Dynorphin and β-Endorphin following Brain Injury

Abstract

Pial artery constriction following fluid percussion brain injury (FPI) is associated with elevated CSF dynorphin and β-endorphin concentration in newborn pigs. Additionally, dynorphin is a dilator under control conditions and a vasoconstrictor under decreased cerebrovascular tone conditions. Vasopressin contributes to β-endorphin-induced pial constriction and the constrictor potential for dynorphin. Recently, it has been observed that FPI reverses vasopressin from a dilator to a constrictor. The present study was designed to characterize the effect of FPI on β-endorphin-induced constriction and the role of vasopressin in that constriction as well as in the reversal of dynorphin's vascular response following FPI. Brain injury of moderate severity (1.9–2.3 atm) was produced in anesthetized newborn pigs equipped with a closed cranial window. Dynorphin in physiologic and pharmacologic concentrations (10⁻¹⁰, 10⁻⁸, 10⁻⁶ M) was reversed from a dilator to a constrictor following FPI (7 ± 1, 11 ± 1, and 16 ± 1 vs −4 ± 1, −7 ± 1, and −11 ± 1% before and after FPI, respectively). Dynorphin-induced vascular changes were accompanied by increased cortical periarachnoid CSF vasopressin and these biochemical changes were potentiated following FPI (24 ± 4 vs 134 ± 7 and 53 ± 7 vs 222 ± 14 pg/mL for control and dynorphin (10⁻⁶ M) before and after FPI, respectively). In contrast, in animals pretreated with the vasopressin receptor antagonist [1-(β-mercapto-ββ-cyclopentamethylene propionic acid) 2-(O-methyl)-Tyr-AVP] (MEAVP, 5 μg/kg iv), dynorphin-induced constriction following FPI was attenuated (6 ± 1, 12 ± 1, and 16 ± 1, vs −2 ± 1, −4 ± 1, and −7 ± 1% before and after FPI, respectively). Additionally, β-endorphin-induced pial constriction was potentiated following FPI (−7 ± 1, −10 ± 1, −15 ± 1 vs −10 ± 1 −15 ± 2, and −21 ± 2% for β-endorphin (10⁻¹⁰, 10⁻⁸, 10⁻⁶ M) before and after FPI, respectively), βendorphin-induced CSF vasopressin release was similarly potentiated following FPI. Further, MEAVP blunted the augmented constrictor responses to β-endorphin observed following FPI (−5 ± 1, −9 ± 1, −14 ± 1 vs −2 ± 1, −5 ± 1, and −8 ± 1% before and after FPI, respectively). These data indicate that FPI potentiates β-endorphin-induced pial construction and reverses dynorphin from a dilator to a constrictor. Additionally, these data show that vasopressin contributes to augmented β-endorphin pial constriction and the reversal of dynorphin's vascular effects following FPI. Further, since CSF dynorphin and β-endorphin concentrations are increased following FPI, these data suggest that these two opioids contribute to pial artery constriction observed following FPI, at least, in part, via the release of vasopressin.