Exp Physiol 95.2 pp 251–262 251 Experimental Physiology – Hot Topic Review Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balance

Respiratory-induced changes in the partial pressures of arterial carbon dioxide (PaCO2) and oxygen (PaO2) play a major role in cerebral blood flow (CBF) regulation. Elevations in PaCO2 (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in PaCO2 (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in PaO2 (hypoxia) below a certain threshold (<40–45mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2–3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases PaO2 and reduces PaCO2, collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors.Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balanc