High altitude, hypoxic-induced modulation of noradrenergic-mediated responses in fetal and adult cerebral arteries.

In response to high altitude long-term hypoxemia, the cerebral arteries of adult and fetal sheep show decreased contractile responses to norepinephrine and other agonists. In this review, we examine some of the presynaptic and postsynaptic contractile mechanisms that might account for these changes. In addition, we examine cerebral vessel relaxation and the role of pregnancy in altering these responses. In general, high altitude hypoxia is associated with augmented or "upregulation" of presynaptic functions. In contrast, postsynaptic functions tend to be significantly depressed or "downregulated." The results emphasize the role of high altitude, long-term hypoxemia in modulating adrenergic-mediated signal transduction in the cerebral vasculature. They specifically highlight the profound differences in acclimatization responses between common carotid and intracranial arteries, as well as the significant differences between responses in the fetus and adult.