We examined the modulation of NMDA-dependent pial arteriolar reactivity by hypoxic hypoxia and normoxic hypercapnia using a cranial window and intravital microscopy in anesthetized piglets. Animals were exposed to 5-15 min of hypoxia or 30 min of hypercapnia with or without indomethacin (10 mg/kg, i.v.) pretreatment Under control conditions, NMDA produced a dose-related dilation of pial arterioles (e.g., 9±1%, 15±2% and 28±5% above me baseline to 10-5, 5×10-5 and 10-4 MNMDA, respectively in the hypoxic group, n=6, P<0.05). After 15 min of hypoxic hypoxia arteriolar responses to 10"4 M NMDA were reduced at 30 min and 1 hr of recovery to 12±5 % and 18±5 %, respectively. Five min of hypoxic hypoxia also reduced dilatation to NMDA, but the effect was more modest. Li contrast, in the indomethacin treated group (n=6), arteriolar responses to NMDA were unchanged following 15 min of hypoxia (PO.05). However, arteriolar responses to NMDA were preserved during and after hypercapnia (n=7). We conclude that severe hypoxic hypoxia and reventilation, but not respiratory acidosis, impairs the NMDA-induced dilation of pial arterioles. In addition, the reduced responsiveness of the cerebral blood vessels to the NMDA can be prevented by pretreatment with indomethacin. Supported by NH grants: HL-30260, HL-46558, and HL-50587.
|Publication status||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology