Arteriolar oxygen reactivity: where is the sensor and what is the mechanism of action?

Arterioles in the peripheral microcirculation are exquisitely sensitive to changes in PO2 in their environment: increases in PO2 cause vasoconstriction while decreases in PO2 result in vasodilatation. However, the cell type that senses O-2 (the O-2 sensor) and the signalling pathway that couples changes in PO2 to changes in arteriolar tone (the mechanism of action) remain unclear. Many (but not all) ex vivo studies of isolated cannulated resistance arteries and large, first-order arterioles support the hypothesis that these vessels are intrinsically sensitive to PO2 with the smooth muscle, endothelial cells, or red blood cells serving as the O-2 sensor. However, in situ studies testing these hypotheses in downstream arterioles have failed to find evidence of intrinsic O-2 sensitivity, and instead have supported the idea that extravascular cells sense O-2. Similarly, ex vivo studies of isolated, cannulated resistance arteries and large first-order arterioles support the hypotheses that O-2-dependent inhibition of production of vasodilator cyclooxygenase products or O-2-dependent destruction of nitric oxide mediates O-2 reactivity of these upstream vessels. In contrast, most in vivo studies of downstream arterioles have disproved these hypotheses and instead have provided evidence supporting the idea that O-2-dependent production of vasoconstrictors mediates arteriolar O-2 reactivity, with significant regional heterogeneity in the specific vasoconstrictor involved. Oxygen-induced vasoconstriction may serve as a protective mechanism to reduce the oxidative burden to which a tissue is exposed, a process that is superimposed on top of the local mechanisms which regulate tissue blood flow to meet a tissue's metabolic demand.