Oxygen increases ductus arteriosus smooth muscle cytosolic calcium via release of calcium from inositol triphosphate-sensitive stores. Am J Physiol Lung Cell Mol Physiol 288: L917-L923, 2005. First published February 4, 2005 doi:10.1152 doi:10. /ajplung.00403.2004 shunts away from the lungs via the ductus arteriosus (DA) and the foramen ovale. After birth, the DA closes concomitant with increased oxygen tension. The present experimental series tests the hypothesis that oxygen directly increases DA smooth muscle cell (SMC) cytosolic calcium ([Ca 2ϩ ]i) through inactivation of a K ϩ channel, membrane depolarization, and entry of extracellular calcium. To test the hypothesis, DA SMC were isolated from late-gestation fetal lambs and grown to subconfluence in primary culture in low oxygen tension (25 Torr). DA SMC were loaded with the calcium-sensitive fluorophore fura-2 under low oxygen tension conditions and studied using microfluorimetry while oxygen tension was acutely increased (120 Torr). An acute increase in oxygen tension progressively increased DA SMC [Ca 2ϩ ]i by 11.7 Ϯ 1.4% over 40 min. ]i via release of calcium from intracellular calcium stores, and subsequent entry of extracellular calcium, and 2) potentiates the effect of contractile agonists. Prolonged patency of the DA may result from disordered intracellular calcium homeostasis. oxygen sensing; pulmonary hypertension potassium channels; vascular biology IN THE FETAL PULMONARY CIRCULATION oxygen tension and nitric oxide production are low (13). Fetal pulmonary blood flow is limited, and blood pressure is high. Blood is shunted away from the lungs through the foramen ovale and the ductus arteriosus (DA), a structure that connects the pulmonary artery to the aorta in utero. At birth, pulmonary blood flow immediately increases by 8-to 10-fold, and pulmonary blood pressure decreases by 50% within the initial 24 h of life (24). An acute increase in oxygen tension causes perinatal pulmonary vasodilation (3, 26), even while it results in constriction of the DA (1, 5). Initial closure of the DA in response to an increase in PO 2 is caused by vessel constriction (14), whereas long-term closure is accomplished through cell migration, apoptosis (25), and cell proliferation (4, 15, 18).In the fetal state, elevation of pulmonary vascular tone and patency of the DA is of critical importance. How pulmonary vascular tone remains elevated while DA tone remains low despite being adjacent vascular structures is unknown. In the fetal pulmonary circulation, endothelin, a powerful vasoconstrictor (29) produced by the endothelial cell (20), plays a key role in maintaining elevated tone, as endothelin inhibition results in sustained fetal pulmonary vasodilation without affecting either pulmonary or aortic pressures (17). This observation suggests that endothelin possesses site-specific properties in the fetal circulation. Whether the low oxygen tension environment of the normal fetus enables endothelin to modulate perinatal pulmonary vascular tone without affecting DA ...