DIFFERENTIAL-EFFECTS OF SHORT-TERM HYPOXIA AND HYPERCAPNIA ON N-METHYL-D-ASPARTATE-INDUCED CEREBRAL VASODILATATION IN PIGLETS

Background and Purpose Recent studies in piglets show that either asph yxia or global cerebral ischemia, which combines effects of hypoxia an d hypercapnia, transiently attenuates N-methyl-D-aspartate (NMDA)-indu ced pial arteriolar dilation. The purpose of this study was to determi ne individually the effects of hypoxic hypoxia and normoxic hypercapni a on NMDA-dependent cerebrovascular reactivity. In addition, we examin ed mechanisms involved in reduced cerebral vascular dilation to NMDA. Methods In anesthetized piglets, we examined pial arteriolar diameters using a cranial window and intravital microscopy. Arteriolar response s to topically applied NMDA were determined under control conditions a nd after arterial hypoxia or arterial hypercapnia. In addition, arteri olar responses to NMDA were examined in animals given indomethacin (10 mg/kg IV) or superoxide dismutase (100 U/mL, topical application) bef ore hypoxia. Results Under control conditions, application of NMDA pro duced a dose-related dilation of pial arterioles (eg, 9+/-1% to 10(-5) 15+/-2% to 5x10(-5), and 28+/-5% to 10(-4) mol/L NMDA above baseline, respectively, in the hypoxic group; n=6, P<.05). After transient expo sure to 15 minutes of hypoxic hypoxia, arteriolar responses to NMDA we re reduced at 30 minutes and at 60 minutes (10(-4) moln NMDA dilated b y 12+/-5% and 18+/-5%, respectively; n=6, P<.05). Five minutes of hypo xic hypoxia also reduced dilatation to NMDA. Indomethacin or superoxid e dis mutase preserved arteriolar responses to NMDA after 15 minutes o f hypoxia. Pial arteriolar responses to NMDA remained unimpaired durin g and after hypercapnia. Conclusions Short-term severe hypoxic hypoxia and reventilation impair the NMDA-induced dilatation of pial arteriol es. Respiratory acidosis alone does not modify pial arteriolar reactiv ity to NMDA. The reduced responsiveness of the cerebral blood vessels to NMDA caused by hypoxia appears to be due to action of oxygen radica ls.