Effect of PGE2 on DA tone by EP4 modulating Kv channels with different oxygen tension between preterm and term

Fan, Fenling; Ma, Aiqun; Guan, Youfei; Huo, Jianhua; Zhi, Hu; Tian, Hui; Zhu, Sen; Fan, Lihong

doi:10.1016/j.ijcard.2009.07.045

Cited by 16 publications

(17 citation statements)

References 24 publications

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“…EP4 levels were increased in the later stages of DA maturation. More recently, Fan et al demonstrated that the isolated preterm human DA was less responsive to oxygen in vitro , but that pharmacological inhibition of the EP4 receptor caused potent constriction [140]. A link between EP4 signaling and Kv channels was suggested as an underlying cause for the differential response between term and preterm human DA samples.…”

Section: Molecular Considerations In Pda Pathobiologymentioning

confidence: 99%

Current Perspectives on Pathobiology of the Ductus Arteriosus

Stoller

DeMauro²,

Dagle³

et al. 2012

J Clin Exp Cardiolog

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The ductus arteriosus (DA) shunts blood away from the lungs during fetal life, but at birth this shunt is no longer needed and the vessel rapidly constricts. Postnatal persistence of the DA, patent ductus arteriosus (PDA), is predominantly a detrimental condition for preterm infants but is simultaneously a condition required to maintain systemic blood flow for infants born with certain severe congenital heart defects. Although PDA in preterm infants is associated with significant morbidities, there is controversy regarding whether PDA is truly causative. Despite advances in our understanding of the pathobiology of PDA, the optimal treatment strategy for PDA in preterm infants is unclear. Here we review recent studies that have continued to elucidate the fundamental mechanisms of DA development and pathogenesis.

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Section: Molecular Considerations In Pda Pathobiologymentioning

confidence: 99%

Current Perspectives on Pathobiology of the Ductus Arteriosus

Stoller

DeMauro²,

Dagle³

et al. 2012

J Clin Exp Cardiolog

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“…Moreover, if associated to selective or nonselective NSAID, glucocorticoids have a synergistic action which increase frequency and severity of ductal constriction; its incidence may double, possibly due to glucocorticoid ability to decrease the ductal sensitivity to prostaglandin (Levy et al, ; Takami et al, ). Other experimentally tested substances with proven constrictive action on rat fetuses are retinoic acid (Moise et al, ; Levy et al, ; Wu et al, ; Takami et al, ), antagonists of prostanoid EP4 receptors (Momma et al, ; Fan et al, ; Chen et al, , b), and inhibitors of nitric oxide synthesis (L‐name) (Takizawa et al, ; Keller et al, ; Reese et al, ; Hsu et al, ), the latter with proven effects in humans. Recently, a novel mechanism for sustaining postnatal ductal constriction induced by oxygen has been described, based on activation of the enzyme Rho‐kinase (Kajimoto et al, ).…”

Section: Fetal Ductus Arteriosus and Ductal Constrictionmentioning

confidence: 99%

Prenatal effects of maternal consumption of polyphenol‐rich foods in late pregnancy upon fetal ductus arteriosus

Zielinsky¹,

Busato²

2013

Birth Defects Research Pt C

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Fetal circulation has characteristic features, being morphologically and functionally different from extrauterine circulation. The ductus arteriosus plays a fundamental role in directing the blood flow to fetal inferior body parts. Basically, the ductus arteriosus directs 80–85% of the right ventricular output arising from the superior vena cava, coronary sinus, and a small part from the inferior vena cava to descending aorta. Its histological structure is made up predominantly by a thick muscular layer, differently from the aorta and the pulmonary artery, which increases with gestational age. The fibers have a circumferential orientation, especially at the external layers, facilitating and making effective ductal constriction. These factors may generate lumen alterations which may cause fetal and neonatal complications, such as heart failure, hydrops, neonatal pulmonary hypertension, and even death. Classically, maternal administration of indomethacin and/or other antiinflammatory drugs interfere in prostaglandins metabolism, causing ductal constriction. However, many cases of fetal ductal constriction, as well as of persistent neonatal pulmonary artery hypertension, remain without an established etiology, being referred as “idiopathic.” In recent years, a growing body of evidence has shown that herbs, fruits, nuts, and a wide diversity of substances commonly used in daily diets have definitive effects upon the metabolic pathway of inflammation, with consequent inhibition of prostaglandins synthesis. This antiinflammatory action, especially of polyphenols, when ingested during the third trimester of pregnancy, may influence the dynamics of fetal ductus arteriosus flow. The goal of this review is to present these new observations and findings, which may influence dietary orientation during pregnancy. Birth Defects Research (Part C) 99:256–274, 2013. © 2013 Wiley Periodicals, Inc.

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“…Both Kv -subunits (Kv1.2, Kv1.5, Kv2.1, Kv3.1, Kv4.2, Kv4.3, and Kv9.3) and Kv -subunits have been shown to possess oxygen sensing capabilities [47]. Among them, Kv1.2, Kv1.5, and Kv2.1 are the predominant Kvαsubunit in the human DA, and Kvγ1.2 is a predominant Kvβ-subunit in the pig DA [37,48,49]. Michelakis et al demonstrated that rotenone and antimycin, mitochondrial electron transport chain inhibitors, decreased diffusible redox-mediator (H 2 O 2 ) production and increased potassium current through Kv channels, resulting in relaxation of oxygen-induced constriction of the DA [48].…”

Section: Channelsmentioning

confidence: 99%

“…They also demonstrated that H 2 O 2 , like oxygen, inhibited potassium currents and depolarized DA SMCs. They then concluded that oxygen increases the production of H 2 O 2 through activating the mitochondrial electron transport chain complexes I or III and then inhibiting Kv channel activity in the DA [45,46,[48][49][50].…”

Section: Channelsmentioning

confidence: 99%

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Role of Ion Channels in Ductus Arteriosus Closure

Akaike¹,

Minamisawa

2013

Human Genet Embryol

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The Ductus Arteriosus (DA) is a normal and essential fetal structure that connects the main pulmonary artery and the descending aorta. The DA constriction which occurs immediately after birth is triggered by: (a) an increase in oxygen tension, (b) a dramatic decline in circulating PGE 2 and a promotion of its degradation in the lung, (c) a decrease in the expression of PGE receptors in the DA wall and (d) a decrease in blood pressure within the DA. Ion channels play an essential role in this acute response that is known as functional DA closure. Oxygenation from fetal to neonatal circulation inhibits several potassium channels (voltage-dependent and ATP-dependent), which then leads to membrane depolarization. This depolarization triggers the activation of voltage-dependent calcium channels, and extracellular calcium then enters into the cytosol of smooth muscle cells of the DA. Calcium is also released from the sarcoplasmic reticulum, with a consequent supply provided through store-operated calcium channels. An increase in cytosolic calcium induces DA constriction. Ion channels also play a role in vascular remodeling of the DA, although this has not yet been extensively investigated. Voltage-dependent Land T-type calcium channels promote formation of intimal thickening through an increase in proliferation and migration of DA smooth muscle cells. Current medical treatment for patients with persistent patent DA is limited to cyclooxygenase inhibitors such as indomethacin and ibuprofen. A better understanding of the role of ion channels in vasoconstriction and vascular remodeling of the DA may encourage the design and development of novel pharmacological treatments for patients with patent DA. In this review, we focus on current knowledge on the roles of ion channels in the DA.

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Effect of PGE2 on DA tone by EP4 modulating Kv channels with different oxygen tension between preterm and term

Cited by 16 publications

References 24 publications

Current Perspectives on Pathobiology of the Ductus Arteriosus

Current Perspectives on Pathobiology of the Ductus Arteriosus

Prenatal effects of maternal consumption of polyphenol‐rich foods in late pregnancy upon fetal ductus arteriosus

Role of Ion Channels in Ductus Arteriosus Closure

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