출생 초기 에탄올 투여 흰쥐의 뇌혈류 조절 변동에 대한 Nociceptin의 관여

Abstract

This study aimed to investigate whether nociceptin contributes to the alterations in cerebral blood flow (CBF) regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol twice a day, 2 hr apart, on postnatal 6, 7 and 8 days. The changes in regional CBF (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-week of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin but not with [Nphe¹]nociceptin(1-13)NH₂, a selective competitive nociceptin receptor antagonist, 5 min prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expressions of nociceptin-like immunoreactivity in the dura mater and cerebral cortex, both of which were significantly inhibited by pretreatment with 7-nitroindazole monosodium salt as well as aminoguanidine 5 min prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin deeply contributes to the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.