Redox signaling in hypoxic pulmonary vasoconstriction

Changes in oxygen tension are sensed by a variety of tissues, such as the carotid body, ductus arteriosus (DA), and pulmonary vasculature. In the fetus, hypoxia keeps the DA open and the pulmonary vessels constricted. After birth, hypoxic pulmonary vasoconstriction (HPV) helps to match ventilation and perfusion. HPV is induced by three general mechanisms - influx of calcium into the smooth muscle cells through L-type channels and store-operated channels, release of calcium from the sarcoplasmic reticulum, and sensitization of actin/myosin to a given level of calcium. We show that reducing agents mimic the effects of hypoxia by reducing potassium current, causing membrane depolarization and increasing calcium influx in pulmonary artery smooth muscle cells (PASMCs), while doing exactly the opposite in the DA. On the other hand, oxidizing agents mimic normoxia by increasing potassium current, causing membrane hyperpolarization and reducing cytosolic calcium in PASMCs. They again do the opposite in the DA. As these redox agents elicit the same responses as shifts in oxygen tension, we consider that changes in oxygen may be signaled by changes in redox status.