Influence of brain injury on opioid-induced pial artery vasodilation.
This study was designed to investigate the effect of fluid percussion brain injury on opioid-induced pial artery vasodilation in the newborn pig. Previous observations have shown that brain injury produces pial artery vasoconstriction associated with elevated cerebral spinal fluid (CSF) opioid levels in the piglet. Additionally, opioids produce pial vasodilation that is attenuated by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Methionine enkephalin (Met), an endogenous mu-opioid agonist in physiological and pharmacological concentrations (10(-10), 10(-8), 10(-6) M), produced vasodilation that was attenuated following brain injury (7 +/- 1 vs. 3 +/- 1%, 11 +/- 1 vs. 5 +/- 1% and 16 +/- 1 vs. 8 +/- 1% for 10(-10), 10(-8), 10(-6) M Met before and after injury, respectively, n = 5). Met-induced dilation was associated with increased cortical periarachnoid CSF guanosine 3',5'-cyclic monophosphate (cGMP), and these biochemical changes were blunted by brain injury (342 +/- 12 and 640 +/- 13 fmol/ml vs. 267 +/- 6 and 321 +/- 17 fmol/ml for control and Met 10(-6) M before and after injury, respectively, n = 5). Leucine enkephalin, an endogenous delta-agonist, induced pial dilation and associated changes in CSF cGMP, which were similarly altered by brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorogood
M C
MC
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
Armstead
W M
WM
D000818:Animals; D001794:Blood Pressure; D001930:Brain Injuries / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid; D004723:Endorphins / Q000502:physiology; D005260:Female; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D011957:Receptors, Opioid / Q000502:physiology; D013552:Swine; D014664:Vasodilation; D014949:Wounds, Nonpenetrating / Q000503:physiopathology
D004723:Endorphins; D009294:Narcotics; D011957:Receptors, Opioid; D006152:Cyclic GMP