Acclimatization to chronic
hypoxia involves numerous compensatory changes in many tissues, including blood vessels. The present data demonstrate that in addition to well-documented changes in contractility, chronic
hypoxia also produces important changes in the mechanisms mediating endothelium-dependent vasodilatation. At the level of the endothelium,
hypoxia attenuates endothelial release of NO and this appears to be mediated through reductions in eNOS specific activity; chronic
hypoxia has little effect on eNOS abundance. In contrast, chronic
hypoxia depresses the abundance of sGC, which functions as the downstream vascular receptor for NO released from the endothelium. The decreased abundance of sGC produced by chronic
hypoxia occurs without changes in sGC specific activity and results in decreased rates of NO-induced cGMP synthesis. Nonetheless, the
vasodilator efficacy of NO is enhanced in hypoxic arteries, which suggests that mechanisms downstream from sGC are upregulated by
hypoxia. Consistent with this view, chronic
hypoxia significantly depresses PDE activity, which serves to prolong cGMP half-life and enhance its
vasodilator effects. It remains possible that chronic
hypoxia may also enhance PKG activity and/or the abundance of its substrates; this possibility remains a promising topic for future investigation. Overall, it is important to recognize that the mechanisms of adaptation to chronic
hypoxia identified in the present study may be somewhat unique to adult carotid arteries. Adaptive responses to chronic
hypoxia can vary considerably between small and large arteries, and also between immature and adult arteries . Still, the present data clearly demonstrate that both the endothelium and vascular smooth muscle of major arteries are profoundly influenced by chronic
hypoxia, and thereby participate fully in whole-body adaptation to reduced
oxygen availability.