Heat shock protein modulation of KATPand KCachannel cerebrovasodilation after brain injury

Abstract

Fluid percussion brain injury (FPI) impairs pial artery dilation to activators of the ATP-sensitive (KATP) and calcium-activated (KCa) K+channels. This study investigated the role of heat shock protein (HSP) in the modulation of K+channel-induced pial artery dilation after FPI in newborn pigs equipped with a closed cranial window. Under nonbrain injury conditions, topical coadministration of exogenous HSP-27 (1 μg/ml) blunted dilation to cromakalim, CGRP, and NS-1619 (10−8and 10−6M; cromakalim and CGRP are KATPagonists and NS-1619 is a KCaagonist). In contrast, coadministration of exogenous HSP-70 (1 μg/ml) potentiated dilation to cromakalim, CGRP, and NS-1619. FPI increased the cerebrospinal fluid (CSF) concentration of HSP-27 from 0.051 ± 0.012 to 0.113 ± 0.035 ng/ml but decreased the CSF concentration of HSP-70 from 50.42 ± 8.96 to 30.9 ± 9.9 ng/ml at 1 h postinsult. Pretreatment with topical exogenous HSP-70 (1 μg/ml) before FPI fully blocked injury-induced impairment of cromakalim and CGRP dilation and partially blocked injury-induced impairment of dilation to NS-1619. These data indicate that HSP-27 and HSP-70 contribute to modulation of K+channel-induced pial artery dilation. These data suggest that HSP-70 is an endogenous protectant of which its actions may be unmasked and/or potentiated with exogenous administration before brain injury.