Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit.

Nakanishi, Toshio; Gu, Hong; Hagiwara, Nobuhisa; Momma, Kazuo

doi:10.1161/01.res.72.6.1218

Cited by 86 publications

(65 citation statements)

References 27 publications

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“…Functional closure of the ductus lumen after birth is primarily due to smooth muscle constriction, 12 with an increase in intracellular calcium concentration contributing to constriction of the ductus arteriosus. 13 Magnesium acts as a calcium antagonist, blocking calcium ion entry into the smooth muscles.…”

Section: Discussionmentioning

confidence: 99%

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

et al. 2010

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Objective: The aim of this study is to evaluate the influence of antenatal magnesium sulfate (MgSO 4 ) treatment on the clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis and on that of symptomatic patent ductus arteriosus (sPDA) to indomethacin treatment in premature neonates.Study Design: This is a retrospective study of 160 consecutively admitted neonates with a gestational age of <28 weeks (41 MgSO 4 exposed and 119 controls) who received indomethacin prophylaxis.Result: Incidence of early closure of the ductus arteriosus was lower in the MgSO 4 -exposed neonates than in the control group (59 vs 84%, respectively; P ¼ 0.002), whereas incidence of an sPDA was higher (46 vs 24%, respectively; P ¼ 0.006). Response to indomethacin treatment was similar between the two groups. Logistic regression analysis indicated increased risk of failure of early ductus arteriosus closure following antenatal MgSO 4 treatment (odds ratio, 4.03; P ¼ 0.002). Conclusion:In extremely preterm neonates, antenatal MgSO 4 treatment reduces clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis but not that of sPDA to indomethacin treatment.

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Section: Discussionmentioning

confidence: 99%

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

et al. 2010

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“…(Pediatr Res 62: 167-169, 2007) P remature infants have an increased incidence of PDA after birth. Although in vitro studies have shown that ductus arteriosus patency may be affected by local concentrations of oxygen, prostaglandins, nitric oxide, endothelin, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate, adenosine, and intracellular potassium and calcium ions (K ϩ and Ca 2ϩ ) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), in vivo studies suggest that postnatal constriction is primarily determined by a shift in the balance between oxygen (a ductus constrictor) and prostaglandins and nitric oxide (ductus dilators) (11,12). Alterations in antenatal glucocorticoid concentrations and postnatal pulmonary vascular resistance also play roles in in vivo ductus constriction (13,14).…”

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confidence: 99%

The Effects of Caffeine on the Preterm Sheep Ductus Arteriosus

Clyman

Roman

2007

Pediatr Res

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Caffeine and other methyl xanthines are widely used in the neonatal period. A recent, randomized, placebo-controlled, multicenter trial found that infants who were randomly assigned to caffeine treatment had less need for pharmacologic and/or surgical closure of a patent ductus arteriosus (PDA). We hypothesized that the decreased need for pharmacologic and surgical closure of the PDA after caffeine treatment might be due to a direct effect of caffeine on ductus contractility. We examined preterm fetal lamb ductus arteriosus (from 24 fetuses, 105 Ϯ 4 d of gestation, term ϭ 147 d), in vitro to determine the direct effects of caffeine on the isometric tension of the ductus arteriosus. Caffeine (0.003-0.3 mM) had no direct effect on ductus arteriosus tension, nor did it affect the contractile response of the ductus arteriosus to increasing oxygen concentrations. Caffeine's lack of effect was observed in both the presence and absence of indomethacin and N g -nitro-L-arginine methyl ester (L-NAME) (inhibitors of prostaglandin and nitric oxide production). In conclusion, we found no evidence of a direct effect of therapeutic caffeine concentrations on ductus contractility. ) (1-10), in vivo studies suggest that postnatal constriction is primarily determined by a shift in the balance between oxygen (a ductus constrictor) and prostaglandins and nitric oxide (ductus dilators) (11,12). Alterations in antenatal glucocorticoid concentrations and postnatal pulmonary vascular resistance also play roles in in vivo ductus constriction (13,14).Recently, a randomized, placebo-controlled, multicenter trial was performed to evaluate the effects of caffeine administration in preterm infants (15). Infants were enrolled in the trial during the first 10 d after birth, and the primary goal of the study was to evaluate the long-term effects of caffeine on neurodevelopmental outcome. An unexpected finding of the study was that infants who were randomly assigned to caffeine treatment had less need for pharmacologic and/or surgical closure of a PDA.Caffeine has been found to directly affect several of the signaling molecules that are involved in ductus constriction: it increases cAMP by inhibiting cyclic nucleotide phosphodiesterase (16); it releases Ca 2ϩ from the endoplasmic reticulum by binding to the ryanodine receptor (17); it inhibits both prostaglandin production (18) and activity (19) and inhibits adenosine activity by binding to its receptors (20). At therapeutic concentrations, caffeine's effects appear to be due primarily to antagonism of the adenosine receptor (21).In this study, we hypothesized that the decreased need for pharmacologic and surgical closure of the PDA after caffeine treatment might be due to a direct effect of caffeine on ductus contractility. To examine this hypothesis, we studied the effects of caffeine on the isolated preterm fetal sheep ductus arteriosus. METHODSPreterm fetal lambs (mixed Western breed: 105 Ϯ 4 d of gestation, term ϭ 147) were delivered by cesarean section and anesthetized with keta...

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“…Our previous study demonstrated that among L-type calcium channels, Cav1.2 was predominant isoform and expression level of Cav1.2 was higher in the rat DA than in the aorta (Yokoyama et al, 2006a). Calcium influx through Ttype voltage-dependent calcium channels, especially Cav3.1, also promoted oxygenation-induced DA constriction (Nakanishi et al, 1993;Akaike et al, 2009).…”

Section: -1 Oxygen-induced Contractionmentioning

confidence: 95%

“…The increase in oxygen tension inhibits ductal smooth muscle voltagedependent potassium channels (Michelakis et al, 2000;Reeve et al, 2001), such as Kv1.5 and Kv2.1, which results in membrane depolarization, an influx of calcium and DA constriction (Nakanishi et al, 1993;Leonhardt et al, 2003). The inhibition of potassium channels is associated with production of diffusible redox mediator (H2O2) by a mitochondrial O2-sensor, electron transport chain complexes I or III in the DA (Archer et al, 2004).…”

Section: -1 Oxygen-induced Contractionmentioning

confidence: 99%

“…The inhibition of potassium channels is associated with production of diffusible redox mediator (H2O2) by a mitochondrial O2-sensor, electron transport chain complexes I or III in the DA (Archer et al, 2004). It has been reported that ATP-sensitive potassium channel was inhibited by the raising oxygen tension, resulting in membrane depolarization (Nakanishi et al, 1993). In addition to involvement of potassium channels, recent study reported that depolarization-independent DA contraction is caused by release of calcium from the IP3-sensitive store in the sarcoplasmic reticulum.…”

Section: -1 Oxygen-induced Contractionmentioning

confidence: 99%

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Regulation of vascular tone and remodeling of the ductus arteriosus

Yokoyama

Minamisawa

Ishikawa

2010

J. Smooth Muscle Res.

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The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The DA is a normal and essential fetal structure. However, it becomes abnormal if it remains patent after birth. Closure of the DA occurs in two phases: functional closure of the lumen within the first hours after birth by smooth muscle constriction, and anatomic occlusion of the lumen over the next several days due to extensive neointimal thickening in human DA. There are several events that promote the DA constriction immediately after birth: (a) an increase in arterial oxygen tension, (b) a dramatic decline in circulating prostaglandinE2 (PGE2), (c) a decrease in blood pressure within the DA lumen, and (d) a decrease in the number of PGE2 receptors in the DA wall. Anatomical closure of the DA is associated with the formation of intimal thickening, which are characterized by (a) an area of subendothelial deposition of extracellular matrix, (b) the disassembly of the internal elastic lamina and loss of elastic fiber in the medial layer, and (c) migration into the subendothelial space of undifferentiated medial smooth muscle cells. In addition to the well-known vasodilatory role of PGE2, our findings uncovered the role of PGE2 in anatomical closure of the DA. Chronic PGE2-EP4-cyclic AMP (cAMP)-protein kinase A (PKA) signaling during gestation induces vascular remodeling of the DA to promote hyaluronan-mediated intimal thickening and structural closure of the vascular lumen. A novel target of cAMP, Epac, has an acute promoting effect on smooth muscle cell migration without hyaluronan production and thus intimal thickening in the DA. Both EP4-cAMP downstream targets, Epac and PKA, regulate vascular remodeling in the DA.

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Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit.

Cited by 86 publications

References 27 publications

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates

The Effects of Caffeine on the Preterm Sheep Ductus Arteriosus

Regulation of vascular tone and remodeling of the ductus arteriosus

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