Brain Injury Impairs ATP-Sensitive K + Channel Function in Piglet Cerebral Arteries

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Abstract
Background and Purpose Traumatic injury is the leading cause of death for infants and children, and mortality is increased with head injury. Previous studies have shown that pial arteries constricted and that responses to several nitric oxide (NO)–dependent dilator stimuli were blunted after fluid percussion injury (FPI) in newborn pigs. Membrane potential of vascular muscle is a major determinant of vascular tone, and activity of K + channels is a major regulator of membrane potential. Recent data show that the NO releasers sodium nitroprusside (SNP) and S-nitroso- N -acetylpenicillamine (SNAP) and 8-bromo-cGMP elicit dilation via ATP-sensitive K + channel (K ATP ) activation. The present study was designed to investigate the effect of FPI on K ATP channel function. Methods Chloralose-anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device that consisted of a saline-filled cylindrical reservoir and a metal pendulum. Brain injury of moderate severity (1.9 to 2.1 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Pial artery diameter was measured with a video microscaler. Data were analyzed by repeated measures ANOVA. An α level of P <.05 was considered significant. Results FPI blunted dilation to cromakalim (10 −8 , 10 −6 mol/L), a K ATP agonist (10±1% and 27±2% versus 3±1% and 7±2% before and after FPI, respectively, n=8). Similarly, FPI blunted dilation to calcitonin gene–related peptide, an endogenous K ATP activator. FPI also blunted dilator responses to SNP, S-nitroso- N -acetylpenicillamine, and 8-bromo-cGMP (10 −6 to 10 −8 mol/L) (10±1% and 20±1% versus 2±1% and 8±2% for SNP before and after FPI; 9±1% and 16±1% versus 2±1% and 4±1% for 8-bromo-cGMP before and after FPI, respectively, n=8). In contrast, responses to papaverine and brain natriuretic peptide were unchanged after FPI. Conclusions These data show that K ATP channel function is impaired after FPI. Furthermore, these data suggest that impaired function of mechanisms distal to NO synthase contribute to altered cerebral hemodynamics after FPI.