Role of Ion Channels in Ductus Arteriosus Closure

Akaike, Toru; Minamisawa, Susumu

doi:10.4172/2161-0436.1000116

Cited by 2 publications

(1 citation statement)

References 67 publications

(96 reference statements)

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“…2). 92 Depletion of Ca 2+ in the SR activates SOCC, which further increases Ca 2+ influx. 32,79 Both non-selective endothelin receptor antagonists in rats, and ET A antagonists in lambs have been found to inhibit spontaneous DA constriction.…”

Section: Patency Of the Da In The Fetusmentioning

confidence: 99%

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Hundscheid¹,

Broek

Lee³

et al. 2019

Pediatr Res

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The ductus arteriosus (DA) is probably the most intriguing vessel in postnatal hemodynamic transition. DA patency in utero is an active state, in which prostaglandin E 2 (PGE 2) and nitric monoxide (NO), play an important role. Since the DA gets programmed for postnatal closure as gestation advances, in preterm infants the DA frequently remains patent (PDA). PGE 2 exposure programs functional postnatal closure by inducing gene expression of ion channels and phosphodiesterases and anatomical closure by inducing intimal thickening. Postnatally, oxygen inhibits potassium and activates calcium channels, which ultimately leads to a rise in intracellular calcium concentration consequently inducing phosphorylation of the myosin light chain and thereby vasoconstriction of the DA. Since ion channel expression is lower in preterm infants, oxygen induced functional vasoconstriction is attenuated in comparison with full term newborns. Furthermore, the preterm DA is more sensitive to both PGE 2 and NO compared to the term DA pushing the balance toward less constriction. In this review we explain the physiology of DA patency in utero and subsequent postnatal functional closure. We will focus on the pathobiology of PDA in preterm infants and the (un)intended effect of antenatal exposure to medication on both fetal and neonatal DA vascular tone.

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Section: Patency Of the Da In The Fetusmentioning

confidence: 99%

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Hundscheid¹,

Broek

Lee³

et al. 2019

Pediatr Res

View full text Add to dashboard Cite

show abstract

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

Ovalı

2020

Front. Pediatr.

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Failure of ductus arteriosus closure after preterm birth is associated with significant morbidities. Ductal closure requires and is regulated by a complex interplay of molecular and mechanical mechanisms with underlying genetic factors. In utero patency of the ductus is maintained by low oxygen tension, high levels of prostaglandins, nitric oxide and carbon monoxide. After birth, ductal closure occurs first by functional closure, followed by anatomical remodeling. High oxygen tension and decreased prostaglandin levels mediated by numerous factors including potassium channels, endothelin-1, isoprostanes lead to the contraction of the ductus. Bradykinin and corticosteroids also induce ductal constriction by attenuating the sensitivity of the ductus to PGE2. Smooth muscle cells of the ductus can sense oxygen through a mitochondrial network by the role of Rho-kinase pathway which ends up with increased intracellular calcium levels and contraction of myosin light chains. Anatomical closure of the ductus is also complex with various mechanisms such as migration and proliferation of smooth muscle cells, extracellular matrix production, endothelial cell proliferation which mediate cushion formation with the interaction of blood cells. Regulation of vessel walls is affected by retinoic acid, TGF-β1, notch signaling, hyaluronan, fibronectin, chondroitin sulfate, elastin, and vascular endothelial cell growth factor (VEGF). Formation of the platelet plug facilitates luminal remodeling by the obstruction of the constricted ductal lumen. Vasa vasorum are more pronounced in the term ductus but are less active in the preterm ductus. More than 100 genes are effective in the prostaglandin pathway or in vascular smooth muscle development and structure may affect the patency of ductus. Hemodynamic changes after birth including fluid load and flow characteristics as well as shear forces within the ductus also stimulate closure. Current pharmacological treatment for the closure of a patent ductus is based on the blockage of the prostaglandin pathway mainly through COX or POX inhibition, albeit with some limitations and side effects. Further research for new agents aiming ductal closure should focus on a clear understanding of vascular biology of the ductus.

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Role of Ion Channels in Ductus Arteriosus Closure

Cited by 2 publications

References 67 publications

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

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