Global ischemia impairs ATP-sensitive K+ channel function in cerebral arterioles in piglets.

Background And Purpose: Indirect evidence from studies in which calcitonin gene-related peptide was used indicates that anoxic stress suppresses functioning of cerebral vascular ATP-sensitive K+ channels. The purpose of this study was to directly examine effects of total global ischemia on cerebral arteriolar dilator responses to activators of ATP-sensitive K+ channels.

Methods: We measured pial arteriolar diameters in anesthetized piglets using a closed cranial window and intravital microscopy. Baseline diameters were approximately 100 microns. Arteriolar responses to aprikalim (10(-8) and 10(-6) mol/L), a pharmacological activator of ATP-sensitive K+ channels, and iloprost (0.1 and 1 microgram/mL), a physiological activator of these channels, were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure.

Results: Before ischemia, aprikalim dilated cerebral arterioles by 7 +/- 2% at 10(-8) mol/L and by 25 +/- 4% at 10(-6) mol/L (n = 5). At 1 hour after ischemia, aprikalim did not cause significant dilation at either dose (3 +/- 2% at 10(-8) mol/L and 7 +/- 4% at 10(-6) mol/L; P < .05 compared with corresponding preischemic response). Arteriolar dilation returned toward normal values at 2 and 4 hours. Similar results were found with iloprost. Furthermore, prior treatment with indomethacin (5 mg/kg) preserved normal arteriolar dilation to aprikalim and iloprost after ischemia. In contrast, arteriolar dilator responses to prostaglandin E2 were intact after ischemia.

Conclusions: Ischemia transiently eliminates cerebral arteriolar dilation to activation of ATP-sensitive K+ channels; arteriolar responses are suppressed at 1 hour and return toward normal over 2 to 4 hours. In addition, reduced responsiveness can be prevented by prior treatment with indomethacin.