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 about its biochemical mechanism and its exact physiological function. Recent work suggests an important role for pulmonary arteriolar smooth muscle cell oxygen-sensitive voltage-dependent potassium channels. Inhibition of these channels by decreased PO2 inhibits outward potassium current, causing membrane depolarization, and calcium entry through voltage-dependent calcium channels. Endothelium-derived vasoconstricting and vasodilating mediators modulate this intrinsic smooth muscle cell reactivity to hypoxia. However, refined modeling of hypoxic pulmonary vasoconstriction operating as a feedback mechanism in inhomogeneous lungs, using more realistic stimulus-response curves and confronted with direct measurements of regional blood flow distribution, shows a more effective than previously assessed ability of this remarkable intrapulmonary reflex to improve gas exchange and arterial oxygenation. Further studies could show clinical benefit of pharmacological manipulation of hypoxic pulmonary vasoconstriction, in circumstances of life-threatening hypoxemia.

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