Heat shock protein modulation of KATP and KCa channel cerebrovasodilation after brain injury.
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.
Armstead
William M
WM
Department of Anesthesia, University of Pennsylvania, 3620 Hamilton Walk, Rm. 305 John Morgan, Philadelphia, PA 19104, USA. armsteaw@uphs.upenn.edu
Hecker
James G
JG
D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001794:Blood Pressure; D001930:Brain Injuries / Q000188:drug therapy / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D010841:Pia Mater / Q000098:blood supply; D015221:Potassium Channels / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001562:Benzimidazoles; D015220:Calcium Channels; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; C086491:NS 1619; D015740:Calcitonin Gene-Related Peptide