Lung capillaries raise the hypoxia alarm

Abstract

When ventilation is blocked, the lung can protect against the loss of blood oxygenation by activating localized arterial vasoconstriction, reducing blood flow to underventilated regions, and redirecting flow to better-ventilated alveoli. This phenomenon, hypoxic pulmonary vasoconstriction (HPV), preserves the overall efficiency of blood oxygenation, but the mechanism by which the hypoxic signal is transmitted to the smooth muscle that contracts the arterioles has remained largely a mystery. In this issue of the JCI, Wang et al. reveal that the endothelial lining of the hypoxic alveoli plays a key role in sensing hypoxia and transmitting the signal to initiate HPV.

Figure 1. Essential features of the capillary mechanism of HPV.

Mixed venous blood flows in through the pulmonary artery that branches to arterioles and then alveolar capillaries. The vascular smooth muscle investment ends at the level of the arterioles. The capillaries surround the air-filled alveolus. (A) In the normally ventilated alveolus, the hypoxic blood (blue) becomes oxygenated (red) and leaves the lung through the pulmonary veins. (B) Blockade of ventilation by airway disease causes alveolar hypoxia. The capillary endothelium is depolarized. The resulting increase of endothelial Ca²⁺ is communicated through endothelial gap junctions to smooth muscle surrounding upstream arterioles. Smooth muscle activation causes arteriolar constriction, restricting blood flow in the underventilated region.