EFFECTS OF ISCHEMIA ON CEREBROVASCULAR RESPONSES TO N-METHYL-D-ASPARTATE IN PIGLETS

We examined the effects of total global ischemia on cerebral arteriola r responses to N-methyl-D-aspartate (NMDA) in anesthetized newborn pig s. Arteriolar responses to 10(-4) M NMDA were determined before and af ter 10 or 20 min of ischemia caused by increasing intracranial pressur e. Before ischemia, NMDA dilated arterioles by 30 +/- 5% (baseline = 8 8 +/- 2 mu m; n = 6). However, after 10 min of ischemia, arteriolar di lation was reduced to 10 +/- 3% at 1 h (P < 0.05). At 2 and 4 h, NMDA- induced dilation was not different from preischemia values. Twenty min utes of ischemia had similar effects. Coadministration of 100 U/ml of superoxide dismutase did not restore arteriolar dilation to NMDA at 1 h after ischemia. Sodium nitroprusside dilated by 14 +/- 3 and 40 +/- 5% at 10(-6) and 10(-5) M before ischemia, respectively, and arteriola r responsiveness was not changed by ischemia (n = 6). Cortical nitric oxide synthase (NOS) activity, measured by the in vitro conversion of L-[C-14]arginine to L-[C-14]citrulline, was unaffected by ischemia (n = 12). We conclude that decreases in cerebral arteriolar responsivenes s to NMDA are not due to impairment of NOS activity, enhanced degradat ion or chelation of nitric oxide (NO), or reduced vascular smooth musc le responsiveness to NO.