Evidence against a role for lipoxygenase-derived products of arachidonic acid in the lamb ductus arteriosus

1982 ◽  
Vol 60 (3) ◽  
pp. 345-349 ◽  
Author(s):  
F. Coceani ◽  
V. M. Jhamandas ◽  
E. Bodach ◽  
J. Labuc ◽  
P. M. Olley ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Oxygen Tension ◽  
Ductus Arteriosus ◽  
Prostaglandin E ◽  
Cyclooxygenase Inhibitor ◽  
Hypoxic Conditions ◽  
Leukotriene Antagonist

The effects of leukotrienes, the leukotriene antagonist FPL55712 (sodium 7-(3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate), and inhibitors of arachidonate lipoxygenase and cyclooxygenase (compound BW755C, 3-amino-1-(m-(trifluoromethyl)-phenyl)-2-pyrazoline; ETYA, 5,8,11,14-eicosatetraynoic acid) were studied in an isolated preparation of ductus arteriosus from mature foetal lambs. Leukotrienes (LT) C4 and D4 produced a modest relaxation of the ductus but only at the highest concentrations tested (10−7 to 10−6 M) and under hypoxic conditions ([Formula: see text], 6–9 Torr (1 Torr = 133.322 Pa)). LTB4 had no effect at any concentration tested. BW755C (10−6 to 10−5 M) and FPL55712 (10−5 M) contracted the hypoxic ductus; however, their action was abolished by pretreatment of the tissue with the cyclooxygenase inhibitor indomethacin (2.8 × 10−6 M). Indomethacin-treated preparations were also unresponsive to ETYA 3 × 10−5 M. The contraction of hypoxic tissues to either BW755C or FPL55712 increased further upon raising the oxygen tension of the medium ([Formula: see text] 591–691 Torr). These findings indicate that leukotrienes and allied compounds formed from lipoxygenase-catalysed reactions do not contribute to prenatal patency of the ductus and are unlikely to have a role in its closure at birth. It is also confirmed that prostaglandin E2 is essential for keeping the vessel patent in the foetus.

Opposite effects of redox status on membrane potential, cytosolic calcium, and tone in pulmonary arteries and ductus arteriosus

2004 ◽  
Vol 286 (1) ◽  
pp. L15-L22 ◽  
Author(s):  
Andrea Olschewski ◽  
Zhigang Hong ◽  
Douglas A. Peterson ◽  
Daniel P. Nelson ◽  
Valerie A. Porter ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Oxygen Tension ◽  
Potassium Current ◽  
Ductus Arteriosus ◽  
Pulmonary Arteries ◽  
Cytosolic Calcium ◽  
Redox Status ◽  
Hypoxic Conditions ◽  
Potent Vasodilator ◽  
Oxygen Signaling

At birth, associated with the rise in oxygen tension, the pulmonary arteries (PA) dilate and the ductus arteriosus (DA) constricts. Both PA and DA constrict with vasoconstrictors and dilate with vasodilators. They respond in a contrary manner only to changes in oxygen tension. We hypothesized that the effects of changes in oxygen are mediated by changes in redox status. Consequently, we tested whether a reducing agent, DTT, and an oxidizing agent, dithionitrobenzoic acid (DTNB), would have opposite effects on a major oxygen signaling pathway in the PA and DA smooth muscle cells (SMCs), the sequence of change in potassium current ( IK), membrane potential ( Em), cytosolic calcium, and vessel tone. Under normoxic conditions, DTT constricted adult and fetal resistance PA rings, whereas in DA rings DTT acted as a potent vasodilator. In normoxia, voltage-clamp measurements showed inhibition of IK by DTT in PASMCs and, in contrast, activation in DASMCs. Consequently, DTT depolarized fetal and adult PASMCs and hyperpolarized DASMCs. [Ca2+]i was increased by DTT in fetal and adult PASMCs and decreased in DASMCs. Under hypoxic conditions, DTNB constricted DA rings and caused vasodilatation in fetal PA rings. DTNB inhibited IK and depolarized the cell membrane in DASMCs. In contrast, activation of IK and hyperpolarization was seen in PASMCs. Thus the same redox signal can elicit opposite effects on IK, Em, cytosolic calcium, and vascular tone in resistance PA and the DA. These observations support the concept that redox changes could signal the opposite effects of oxygen in the PA and DA.

Release of prostaglandins from intact fetal lamb ductus arteriosus

1983 ◽  
Vol 61 (5) ◽  
pp. 240-247 ◽  
Author(s):  
C. R. Pace-Asciak ◽  
G. Rangaraj
Keyword(s):  
Gas Chromatography ◽  
Arachidonic Acid ◽  
Ductus Arteriosus ◽  
Significant Proportion ◽  
Calcium Ionophore ◽  
Major Product ◽  
Electron Capture Detection ◽  
Prostaglandin E ◽  
Physiological Importance ◽  
Near Term

Intact rings and slices of ductus arteriosus from fetal lambs near term (130–143 days gestation) were incubated with [14C]arachidonic acid and the fate of the label in the incubation fluid and tissue was followed by thin-layer radiochromatography (TLC). Prostaglandins formed from endogenous stores of arachidonic acid were assayed by capillary gas chromatography with electron-capture detection. In additional experiments, the prelabelled tissue was incubated with various drugs (e.g., angiotensin II, bradykinin, and calcium ionophore) to determine their effects on the release of 14C-labelled prostaglandins. Results indicate that the ductus arteriosus is oriented towards forming prostaglandin (PG) I2, with PGE2 being formed to a minor extent in all studies. While radiochromatographic studies (TLC) suggested a considerable complexity mostly because of overlapping products (PGs and metabolites), this was resolved using gas chromatography where a complete resolution of PGs from these metabolites was observed. In the tissue-labelling experiments most of the radioactivity remained in the incubation fluid and was recovered as unchanged arachidonic acid, although a small but significant proportion of label was observed in a mixture of prostaglandins (4.2 ± 0.6%, n = 16) with 6-keto PGF1α being the major product. The ductus tissue incorporated a small amount of label (3.4 ± 0.4%, n = 19) of which 49.7 ± 4.9% (n = 13) was found in the tissue phospholipids. Hydrolysis of tissue-bound [14C]arachidonic acid, which appeared in the perfusing medium together with 14C-labelled prostaglandins, was in the range of 28.0 ± 2.7% (n = 9) of total tissue radioactivity per experiment. Although 42.2 ± 2.5% (n = 18) of the radioactivity released by each of the drugs represented a mixture of prostaglandins and their metabolites (the rest recovered as arachidonic acid), no appreciable selectivity by any of the drugs was found for either the stimulation of phospholipase activity in this tissue or for the rerouting of the prostaglandin synthetic system to form prostaglandin E2 instead of I2. We conclude that prostaglandin I2 rather than E2 is probably of physiological importance in this unique fetal blood vessel.

Vascular endothelial growth factor polymorphism rs2010963 status does not affect patent ductus arteriosus incidence or cyclooxygenase inhibitor treatment success in preterm infants

2019 ◽  
Vol 29 (7) ◽  
pp. 893-897
Author(s):  
Hannes Sallmon ◽  
Tünay Aydin ◽  
Stefanie Hort ◽  
Anja Kubinski ◽  
Christina Bode ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Patent Ductus Arteriosus ◽  
Ductus Arteriosus ◽  
Treatment Success ◽  
Vascular Endothelial ◽  
Cyclooxygenase Inhibitor ◽  
Endothelial Growth Factor ◽  
Inhibitor Treatment ◽  
Patent Ductus

AbstractBackground:Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults.Aim:Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success.Methods:We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review.Results:We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed.Conclusion:Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.

Prostaglandin E and the Ductus Arteriosus

1985 ◽  
Vol 7 (3) ◽  
pp. 75-76
Keyword(s):  
Smooth Muscle ◽  
Seminal Fluid ◽  
Ductus Arteriosus ◽  
Active Material ◽  
Crystalline Form ◽  
Prostaglandin E ◽  
Chemical Structures ◽  
Soluble Acid ◽  
Derivatives Of ◽  
Widespread Interest

In 1936, Euler of Sweden identified in seminal fluid an active material that contracts smooth muscle; he named this lipid-soluble acid "prostaglandin." More than 20 years passed before the isolation in crystalline form of two prostaglandins, PGE1 and PGE1a, was accomplished. The elucidation of their chemical structures in 1962 by Bergstrom led to their biosynthesis in 1964. Few substances have generated more widespread interest in biologic circles than the prostaglandins. The prostaglandins are derivatives of fatty acids and have been detected in almost every tissue including the fetal ductus. The E-type prostaglandins are powerful vasodilators of nearly all arterioles by direct relaxation of vascular smooth muscle.

Prolonged Prostaglandin E1 Infusion: Histologic Effects on the Patent Ductus Arteriosus

PEDIATRICS ◽  
1981 ◽  
Vol 67 (6) ◽  
pp. 816-819
Author(s):  
Roger B. Cole ◽  
Steven Abman ◽  
Kalim U. Aziz ◽  
Saroja Bharati ◽  
Maurice Lev
Keyword(s):  
Pulmonary Artery ◽  
Prostaglandin E1 ◽  
Mononuclear Cells ◽  
Ductus Arteriosus ◽  
Prostaglandin E ◽  
Cavity Formation ◽  
Prolonged Infusion ◽  
Histologic Study ◽  
Surgical Closure ◽  
The Media

An infant with Ebstein's malformation of the tricuspid valve and severe pulmonic stenosis under-went a 39-day course of prostaglandin E1 infusion, and a histologic study of the ductus arteriosus was undertaken after autopsy. There were marked alterations in the ductal and juxtaductal structures following this prolonged infusion of prostaglandin E1. The internal elastic lamella of the ductus was disrupted in many areas. The media showed widespread areas of disruption with cavity formation. The adventitia adjacent to the junction of the ductus with the pulmonary artery was thickened and infiltrated with mononuclear cells. The nerve trunks in the adventitia were markedly infiltrated with mononuclear cells and showed cavitation as well as considerable surrounding edema. Mucopolysaccharides were increased throughout the ductus. These changes produced increased fragility of the ductal and juxtaductal structures, thus increasing the likelihood of spontaneous aneurysms and rupture, or of tearing or rupture at the aortic and pulmonary junctions at the time of surgical closure of the ductus. Unusual fragility of the ductus, pulmonary artery, and aorta has been observed during ligation of the ductus following prostaglandin E infusions lasting seven and ten days. Additionally, another patient who had received prostaglandin E infusion for six days demonstrated aneurysmal fullness to the ductus arteriosus at autopsy. The histologic findings and intraoperative experience in this study suggest that there may be a real danger of spontaneous neous or surgically related rupture of the ductus arteriosus after prolonged infusion of prostaglandins.

Reduced glutathione modulates the arachidonic acid induced coronary reactions

1984 ◽  
Vol 62 (10) ◽  
pp. 1261-1267 ◽  
Author(s):  
Jaime Talesnik ◽  
James N. Tsoporis
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Reduced Glutathione ◽  
Isolated Heart ◽  
Prostaglandin E ◽  
Guinea Pig Heart ◽  
Rat Hearts ◽  
Resistance Vessels ◽  
Vasodilator Action ◽  
Perfused Hearts

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5–0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.

scholarly journals Identification of differentially regulated genes in human patent ductus arteriosus

2016 ◽  
Vol 241 (18) ◽  
pp. 2112-2118 ◽  
Author(s):  
Pratik Parikh ◽  
Haiqing Bai ◽  
Michael F Swartz ◽  
George M Alfieris ◽  
David A Dean
Keyword(s):  
Cultured Cells ◽  
Ductus Arteriosus ◽  
Coarctation Of The Aorta ◽  
Transient Transfection ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Prostaglandin E ◽  
Promoter Regions ◽  
Mrna Quantitation ◽  
Multiple Patients

In order to identify differentially expressed genes that are specific to the ductus arteriosus, 18 candidate genes were evaluated in matched ductus arteriosus and aortic samples from infants with coarctation of the aorta. The cell specificity of the gene's promoters was assessed by performing transient transfection studies in primary cells derived from several patients. Segments of ductus arteriosus and aorta were isolated from infants requiring repair for coarctation of the aorta and used for mRNA quantitation and culturing of cells. Differences in expression were determined by quantitative PCR using the ΔΔCt method. Promoter regions of six of these genes were cloned into luciferase reporter plasmids for transient transfection studies in matched human ductus arteriosus and aorta cells. Transcription factor AP-2b and phospholipase A2 were significantly up-regulated in ductus arteriosus compared to aorta in whole tissues and cultured cells, respectively. In transient transfection experiments, Angiotensin II type 1 receptor and Prostaglandin E receptor 4 promoters consistently gave higher expression in matched ductus arteriosus versus aorta cells from multiple patients. Taken together, these results demonstrate that several genes are differentially expressed in ductus arteriosus and that their promoters may be used to drive ductus arteriosus-enriched transgene expression.

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