Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure

Hypoxic pulmonary vasoconstriction continues to attract interest more than half a century after its original report because of persistent mystery abou t its biochemical mechanism and its exact physiological function. Recent wo rk suggests an important role for pulmonary arteriolar smooth muscle cell o xygen-sensitive voltage-dependent potassium channels. Inhibition of these c hannels by decreased PO, inhibits outward potassium current, causing membra ne depolarization, and calcium entry through voltage-dependent calcium chan nels. Endothelium-derived vasoconstricting and vasodilating mediators modul ate this intrinsic smooth muscle cell reactivity to hypoxia. However, refin ed modeling of hypoxic pulmonary vasoconstriction operating as a feedback m echanism in inhomogeneous lungs, using more realistic stimulus-response cur ves and confronted with direct measurements of regional blood flow distribu tion, shows a more effective than previously assessed ability of this remar kable intrapulmonary reflex to improve gas exchange and arterial oxygenatio n. Further studies could show clinical benefit of pharmacological manipulat ion of hypoxic pulmonary vasoconstriction, in circumstances of life-threate ning hypoxemia.