Effect of Oxygen
The brain has a very high metabolic demand for oxygen compared to other organs, and thus, it is not surprising that acute hypoxia is a potent dilator in the cerebral circulation that produces marked increases in cerebral blood flow [
163]. In general, blood flow does not change in the brain until tissue
Po
2 falls below ~50 mmHg, below which cerebral blood flow increases substantially [
163]. As hypoxia decreases
Po
2 further, cerebral blood flow can rise up to 400% of resting levels [
164]. Increases in cerebral blood flow do not change metabolism, but hemoglobin saturation falls from ~100% at
Po
2 >70 mmHg to ~50% at
Po
2 <50 mmHg [
164]. Acute hypoxia causes an increase in cerebral blood flow via direct effects on vascular cells of cerebral arteries and arterioles. Hypoxia-induced drop in ATP levels opens K
ATP channels on smooth muscle, causing hyperpolarization and vasodilation [
165]. In addition, hypoxia rapidly increases nitric oxide and adenosine production locally, also promoting vasodilation [
166]. Chronic hypoxia increases cerebral blood flow through an effect on capillary density [
16ā
19] (see
Microcirculation and Neurovascular Unit).
Effect of Carbon Dioxide
Carbon dioxide (CO
2) has a profound and reversible effect on cerebral blood flow, such that hypercapnia causes marked dilation of cerebral arteries and arterioles and increased blood flow, whereas hypocapnia causes constriction and decreased blood flow [
167,
168]. The potent vasodilator effect of CO
2 is demonstrated by the finding that in humans 5% CO
2 inhalation causes an increase in cerebral blood flow by 50% and 7% CO
2 inhalation causes a 100% increase in cerebral blood flow [
168]. Although several mechanisms involved in hypercapnic vasodilation have been proposed, the major mechanism appears to be related to a direct effect of extracellular H
+ on vascular smooth muscle [
169]. This is supported by findings that neither bicarbonate ion nor changes in
Pco
2 alone affect cerebral artery diameter [
170]. Other proposed mechanisms involved in the response to changes in
Pco
2 include vasodilator prostanoids and nitric oxide; however, the involvement of these mediators appears to be species-specific [
171,
172].
Maybe this explains how waking up is possible if the carotid arteries are not compressed good enough.