Oxygen modulation of pulmonary arterial prostacyclin synthesis is developmentally regulated

Shaul, Philip W.; Farrar, M. A.; Magness, Ronald R.

doi:10.1152/ajpheart.1993.265.2.h621

Cited by 22 publications

(27 citation statements)

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“…Although previous investigators have demonstrated a role for calcium release from ryanodine-sensitive stores in umbilical vein endothelial cells (25), the present data are the first to implicate a role for calcium release from ryanodinesensitive stores in the normoxia-induced increase in fetal PAEC [Ca 2ϩ ] i . At birth, PAECs must contract, increase production of NO (8,26) and prostacylin (27,28), and decrease endothelin production (29) to enable effective gas exchange to occur in the lungs. Changing the exposure of PAECs from normoxia to hypoxia reduces reactive oxygen species (ROS) (30,31) so presumably the reverse is also true.…”

Section: Discussionmentioning

confidence: 99%

Acute Normoxia Increases Fetal Pulmonary Artery Endothelial Cell Cytosolic Ca2+ Via Ca2+-Induced Ca2+ Release

et al. 2006

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To test the hypothesis that an acute increase in O 2 tension increases cytosolic calcium ([Ca 2ϩ ] i ) in fetal pulmonary artery endothelial cells (PAECs) via entry of extracellular calcium and subsequent calcium-induced calcium release (CICR) and nitric oxide release, low-passage PAECs (Ͻ10 passages) were isolated from the intralobar pulmonary artery (PA) of fetal sheep and maintained under hypoxic conditions (PO 2 , 25 Torr). Using the calciumsensitive dye fura-2, we demonstrated that acute normoxia (PO 2 ϭ 120 Torr) increased PAECs [Ca 2ϩ ] i by increasing the rate of entry of extracellular calcium. In the presence of either ryanodine or 2-aminoethoxy-diphenylborate (2APB), normoxia did not lead to a sustained increase in PAECs [Ca 2ϩ ] i Whole-cell patch clamp studies demonstrated that acute normoxia causes PAEC membrane depolarization. When loaded with the nitric oxide (NO)-sensitive dye, DAF -FM, acute normoxia increased PAEC fluorescence. In PAECs derived from fetal lambs with pulmonary hypertension, an acute increase in O 2 tension had no effect on either [Ca 2ϩ ] i or NO production. Hypoxia increases loading of acetylcholine-sensitive calcium stores, as hypoxia potentiated the response to acetylcholine We conclude that acute normoxia increases [Ca 2ϩ ] i and NO production in normotensive but not hypertensive fetal PAECs via extracellular calcium entry and calcium release from calcium-sensitive intracellular stores. I n the fetus, pulmonary blood flow is limited. At birth, pulmonary blood flow increases eight-to 10-fold (1) and pulmonary arterial pressure decreases to 50% of systemic levels within 24 h after birth (2). The critical physiologic stimuli that account for perinatal pulmonary vasodilation include rhythmic distention of the lung (3), an increase in both shear stress (4), and oxygen tension (5). In response to physiologic stimuli, the pulmonary endothelium elaborates vasoactive mediators such as NO (6), endothelin (7), bradykinin, and prostaglandins. PAEC NO production is necessary (8), although not always sufficient, for the transition of the pulmonary circulation from a high to low resistance circuit.Vasoactive products produced by the PAECs simultaneously preserve and constrain fetal pulmonary blood flow. During fetal life, inhibition of endothelin, a vasoconstrictive protein produced by the endothelium (7), causes marked pulmonary vasodilation (9). Conversely, inhibition of NO increases pulmonary vascular resistance (8). Among the most important functions of the PAECs is the ability to sense and respond to an increase in oxygen tension at birth. Interestingly, the capacity of the pulmonary circulation to sense and respond to an acute increase in oxygen tension is developmentally regulated. Not until gestation is approximately 85% complete is the fetal pulmonary circulation able to respond to an increase in oxygen tension (10). Vasodilator agents that act through endothelial cell-mediated mechanisms produce only transient pulmonary vasodilation (5,11). Perhaps the relativ...

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Section: Discussionmentioning

confidence: 99%

Acute Normoxia Increases Fetal Pulmonary Artery Endothelial Cell Cytosolic Ca2+ Via Ca2+-Induced Ca2+ Release

et al. 2006

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“…By extension, ET-1 is implicated in the pulmonary constric-tor response to hypoxia [1]. Evidence in support of these concepts has also been obtained by other investigators using a variety of approaches both in vitro [6][7][8][9][10][11][12][13][14][15] and in vivo [15][16][17][18][19][20][21][22]. Nevertheless, the ontogeny of these regulatory mechanisms remains undefined despite the importance, both conceptual and practical, of the problem.…”

Section: Introductionmentioning

confidence: 89%

Contractile and Relaxing Mechanisms in Pulmonary Resistance Arteries of the Preterm Fetal Lamb

Yuan¹,

Theis²,

Coceani³

2000

Neonatology

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Isolated pulmonary resistance arteries from term fetal lambs have nitric oxide (NO)- and prostaglandin-mediated relaxing mechanisms which are activated when PO₂ is raised from fetal to neonatal levels. The same vessels contract under hypoxia, and the contraction has been ascribed to endothelin-1 (ET-1). We have now studied these vasoeffector mechanisms before term (0.7 and 0.65 gestation) with the objective of determining whether their activity correlates with the development of susceptibility to oxygen changes. Experiments were carried out at neonatal PO₂, when expectedly relaxing mechanisms are maximally expressed, or under hypoxia. At either fetal age, the NO synthesis inhibitor, N^G-nitro-L-arginine methyl ester (100 μM), had no effect on basal tone, while indomethacin (2.8 μM) was a weak constrictor. Premature arteries did not contract when first exposed to hypoxia, but they responded marginally to a second exposure. The same arteries contracted strongly to a thromboxane A₂ analogue (ONO-11113, 0.1 μM) and ET-1 (10 nM), while their contraction to activating solution (5 mM Ca²⁺ in K⁺-Krebs solution) was small and variable. At 0.7 gestation, bradykinin (0.1–100 nM), acetylcholine (0.01–10 μM), and sodium nitroprusside (0.1 nM to 10 μM) dose-dependently relaxed arteries precontracted with ONO-11113. Conversely, at 0.65 gestation the relaxation to bradykinin and acetylcholine was not dose-dependent and tended to be weaker. We conclude that preterm pulmonary arteries have viable effector mechanisms for contraction and relaxation. However, the capability for these mechanisms to be activated by PO₂ changes is markedly curtailed.

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“…Увеличение ее содержания цАМФ вызывает релак сацию гладких мышц через фосфорилирование мио зина или активацию калиевых каналов, ведущую к гиперполяризации гладких мышц. Продукция простациклина значительно увеличивается в пос леднем триместре беременности [23], когда несколь ко эндотелий зависимых вазодилататоров, в т. ч. ацетилхолин и брадикинин, увеличивают его синтез в легких плода.…”

Section: онтогенез регуляторных механизмов легочной циркуляции в пренunclassified

Pulmonary blood flow in fetus and newborns

Markov¹

2012

Pulʹmonologiâ (Mosk.)

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Oxygen modulation of pulmonary arterial prostacyclin synthesis is developmentally regulated

Cited by 22 publications

References 0 publications

Acute Normoxia Increases Fetal Pulmonary Artery Endothelial Cell Cytosolic Ca2+ Via Ca2+-Induced Ca2+ Release

Acute Normoxia Increases Fetal Pulmonary Artery Endothelial Cell Cytosolic Ca2+ Via Ca2+-Induced Ca2+ Release

Contractile and Relaxing Mechanisms in Pulmonary Resistance Arteries of the Preterm Fetal Lamb

Pulmonary blood flow in fetus and newborns

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