Hypoxic pulmonary vasoconstriction: cyclic adenosine diphosphate-ribose, smooth muscle Ca(2+) stores and the endothelium.

Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary arteries, and supports ventilation/perfusion matching. However, in diseases such as emphysema, HPV can promote hypoxic pulmonary hypertension (HPH), which ultimately leads to right heart failure. Since it was first described, the mechanisms underpinning HPV have remained obscure, and current therapies for HPH are poor. Previous investigations have suggested that HPV may be mediated by processes intrinsic to the pulmonary artery smooth muscle, and by the release of a vasoconstrictor(s) from the endothelium. It was thought that oxygen-sensitive ion channels in the smooth muscle cell membrane triggered HPV, and it has been argued that the endothelium-derived vasoconstrictor is endothelin-1. However, these proposals remain controversial. This review discusses the regulation by hypoxia of cyclic adenosine diphosphate-ribose production and Ca(2+) release from the sarcoplasmic reticulum in pulmonary artery smooth muscle. The role of these processes in triggering maintained HPV is then related to its subsequent progression due to vasoconstrictor(s) release from the endothelium.