Prolonged hypoxia causes several adaptive changes in systemic physiolo
gy and tissue metabolism. We studied the effects of hypobaric hypoxia
on glucose transport at the blood-brain barrier (BBB) in the rat. We f
ound that hypoxia increased the density of brain microvessels seen on
immunocytochemical stains using an antibody to the glucose transportin
g protein GLUT. In addition, we found that hypoxia increased the densi
ty of GLUT in isolated cerebral microvessels as determined by specific
cytochalasin B binding. The higher GLUT density in isolated cerebral
microvessels was evident after 1 wk of hypoxia and was associated with
decreased activity of gamma-glutamyl-transpeptidase. Consistent with
these findings, we also demonstrated that 3 wk of hypobaric hypoxia ca
used increased unidirectional transport of glucose at the BBB in sever
al brain regions in vivo, as determined by the doubly labeled single-p
ass indicator-fractionation atrial bolus injection method in anestheti
zed rats. We conclude that chronic hypobaric hypoxia is associated wit
h increased glucose transport at the BBB.