Heat shock protein modulation of K_ATPand K_Cachannel cerebrovasodilation after brain injury

Abstract

Fluid percussion brain injury (FPI) impairs pial artery dilation to activators of the ATP-sensitive (K(ATP)) and calcium-activated (K(Ca)) 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 mug/ml) blunted dilation to cromakalim, CGRP, and NS-1619 (10(-8) and 10(-6) M; cromakalim and CGRP are K(ATP) agonists and NS-1619 is a K(Ca) agonist). In contrast, coadministration of exogenous HSP-70 (1 mug/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 mug/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.

Hypoxia and reoxygenation modulate the arrhythmogenic activity of the pulmonary vein and atrium

“…The higher expression of HSP70 in the RA may be caused by the effects of low-oxygenated blood in the RA, and provide protective effects on hypoxia as shown by unchanged AP duration. HSP70 has been shown to promote K ATP function [30] and provide cardioprotective effects in ischaemia [31]. HSP70 may increase transient outward and rapidly activating delayed-rectifier potassium currents [32,18].…”

Blood–brain barrier and traumatic brain injury

“…A neuropeptide in the family of neurokinins, substance P (SP), is a promoter of neuroinflammation as a response to various noxious stimuli (Poncet et al, ; Richardson and Vasko, ; Zacest et al, ), acting on neurokinin 1 receptors (NK1r) and disturbing the normal BBB, leading to increased vascular permeability and interstitial accumulation of osmotically active molecules and water, culminating in the so‐called early vasogenic edema (Bosaller et al, 1992; Donkin et al, ). SP increase is documented immediately after initial trauma, diminishing in the next hours (Armstead et al, ; Donkin et al, ; Song et al, ). Many other peptides, such as calcitonin gene‐related peptide (CGRP), play similar roles in complex cerebral blood flow self‐regulation (Vink et al, ; Psen and Gulati, ).…”

Clinical Implications of Mitochondrial Dysfunction

“…267 Genomic analysis suggests that IPC and APC each reflect a unique pattern of induced gene expression for the synthesis of proapoptotic and antiapoptotic proteins. 277 Other approaches to minimizing cellular injury during periods of oxidative stress or postinjury reperfusion include enhancement of endogenous expression of cytoprotective antioxidants. 269 It remains unclear how many patterns of protective gene expression are possible, but isoflurane pretreatment may also protect cardiac myocytes against apoptosis by increasing the expression of the antiapoptotic protein Bcl-2.…”