Brain injury impairs ATP-sensitive K+ channel function in piglet cerebral arteries.
OBJECTIVE
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 (KATP) activation. The present study was designed to investigate the effect of FPI on KATP 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 alpha level of P < .05 was considered significant.


RESULTS
FPI blunted dilation to cromakalim (10(-8), 10(-6) mol/L), a KATP 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 KATP 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 KATP 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.
Armstead
W M
WM
Department of Anesthesia, University of Pennsylvania, USA.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001769:Blood / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014949:Wounds, Nonpenetrating / Q000378:metabolism*
D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP