ATP-dependent K+ channel activation reduces loss of opioid dilation after brain injury

ATP-dependent K+ (K-ATP) channel function is impaired after fluid percussion brain injury (FPI). Additionally, the nitric oxide (NO) releaser sodium nitroprusside and a cGMP analog elicit pial dilation via K-ATP channel activation, whereas opioids such as methionine enkephalin (Met) elicit pial dilation via NO and K-ATP channel activation. Decremented Met dilation contributes to reductions in pial artery diameter and altered cerebral hemodynamics after FPI. This study was designed to investigate the role of K-ATP channel activation before FPI in the loss of opioid dilation subsequent to FPI in newborn pigs equipped with a closed cranial window. FPI was produced by allowing a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw in the cranium. FPI blunted dilation to Met (7 +/- 1, 11 +/- 1, and 17 +/- 1% before FPI vs. 1 +/- 1, 4 +/- 1, and 6 +/- 1% after FPI for 10(-10), 10(-8), and 10(-6) M Met, respectively). Met-associated elevation in cerebrospinal fluid (CSF) cGMP was similarly blunted (350 +/- 12 and 636 +/- 12 fmol/ml before FPI vs. 265 +/- 5 and 312 +/- 17 fmol/ml after FPI for control and 10(-6) M Met, respectively). In piglets pretreated with cromakalim (10(-10) M) 20 min before FPI, Met dilation was partially restored (7 +/- 1, 10 +/- 1, and 15 +/- 1% before FPI vs. 4 +/- 1, 7 +/- 1, and 11 +/- 1% after FPI for 10(-10), 10(-8), and 10(-6) M Met, respectively). Met cGMP release was similarly partially restored (400 +/- 9 and 665 +/- 25 fmol/ml before FPI vs. 327 +/- 11 and 564 +/- 23 fmol/ml after FPI for control and 10(-6) Met, respectively). Cromakalim (10(-10) M) had no effect on pial diameter itself but prevented pial artery constriction by FPI (148 +/- 5 to 124 +/- 5 mu m vs. 139 +/- 4 to 141 +/- 4 mu m in the absence vs. presence of cromakalim pretreatment, respectively). In contrast, pretreatment with a subthreshold concentration of NS-1619, a calcium-dependent K+ channel agonist, did not restore vascular and biochemical parameters after FPI. These data indicate that prior K-ATP channel activation reduces the loss of opioid dilation after FPI.