We determined whether cerebral arteriolar dilation to N-methyl-d-aspartate (NMDA), a response dependent on stimulation of cortical neurons and inhibited by anoxic stress, would be preserved by hypothermia during and following ischemia. Pial arteriolar diameters in anesthetized piglets were determined via intravital microscopy. Arteriolar responses to NMDA (10, 50, and 100 micromol/l) were measured before and 1 h after 10 min of global ischemia. Piglets were exposed to either total body or selective brain cooling (33-34 degrees C). Arteriolar dilation to lower doses or to 100 micromol/l NMDA was not affected by hypothermia alone (51 +/- 3 vs. 46 +/- 7%, normothermia vs. hypothermia; n = 7) in nonischemic animals. However, arteriolar responses to 100 micromol/l NMDA were clearly attenuated after ischemia despite body cooling during ischemia (53 +/- 3 vs. 32 +/- 6%; n = 8), hypothermia during ischemia and early reperfusion (49 +/- 10 vs. 20 +/- 3%; n = 8), or selective brain cooling (48 +/- 5 vs. 20 +/- 5%; n = 10). In contrast, pretreatment with indomethacin resulted in complete preservation of NMDA-induced vasodilation after ischemia. Thus, hypothermia fails to protect against neuronal dysfunction during ischemia.