Evidence for an effector role of endothelin in closure of the ductus arteriosus at birth

1992 ◽  
Vol 70 (7) ◽  
pp. 1061-1064 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey ◽  
Eric Seidlitz
Keyword(s):  
Oxygen Concentration ◽  
Oxygen Tension ◽  
Ductus Arteriosus ◽  
Critical Role ◽  
Blood Oxygen ◽  
Endothelin 1 ◽  
A Value ◽  
Near Term ◽  
Oxygen Concentrations

The ductus arteriosus is a special muscular shunt that in the fetus allows blood to bypass the unexpanded lungs. It closes rapidly after birth and this event is initiated by the physiologic rise in blood oxygen tension. Endothelin-1 has been proposed by us as a local mediator for oxygen after demonstrating that it is formed within the ductus and is a potent ductus constrictor. To confirm this possibility, we have now measured the release of endothelin-1 from the isolated ductus of near-term fetal lambs at different oxygen concentrations of the medium. In addition, using the same preparation, we have examined the effect on contractile tone of compounds interfering with the synthesis (phosphoramidon, 50 μM) and action (BQ123, 1 μM) of endothelin-1. We report that release of endothelin-1 from the ductus tends to increase with the oxygen concentration up to a value mimicking the neonatal condition. Phosphoramidon and, to a greater degree, BQ123 inhibit the contraction of the vessel to oxygen. These results implicate endothelin-1 as the effector agent for oxygen in the ductus and, by extension, assign to this peptide a critical role in the closure of the vessel at birth.Key words: ductus arteriosus closure, oxygen, endothelin.

scholarly journals Regulation of Ductus Arteriosus Patency by Nitric Oxide in Fetal Lambs: The Role of Gestation, Oxygen Tension, and Vasa Vasorum

1998 ◽  
Vol 43 (5) ◽  
pp. 633-644 ◽  
Author(s):  
Ronald I Clyman ◽  
Nahid Waleh ◽  
Stephen M Black ◽  
R Kirk Riemer ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Tension ◽  
Ductus Arteriosus ◽  
Vasa Vasorum

Endothelin-1 release from lamb ductus arteriosus; relevance to postnatal closure of the vessel

1991 ◽  
Vol 69 (2) ◽  
pp. 218-221 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey
Keyword(s):  
Key Words ◽  
Conformational Change ◽  
Contractile Response ◽  
Ductus Arteriosus ◽  
Endothelin 1 ◽  
Wet Weight ◽  
Presence And Absence ◽  
Near Term ◽  
Cytochrome P 450 ◽  
Postnatal Closure

Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight∙min) both in the presence and absence of the endothelium. Anisomycin (10−4 M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.Key words: ductus arteriosus closure, oxygen, cytochrome P-450, endothelin.

Involvement of intramural prostaglandin E2 in prenatal patency of the lamb ductus arteriosus

1986 ◽  
Vol 64 (6) ◽  
pp. 737-744 ◽  
Author(s):  
Flavio Coceani ◽  
Dayle Huhtanen ◽  
Nancy C. Hamilton ◽  
Isis Bishai ◽  
Peter M. Olley
Keyword(s):  
Release Rate ◽  
Enzyme System ◽  
Reduced Glutathione ◽  
Ductus Arteriosus ◽  
Prostaglandin E ◽  
Concomitant Treatment ◽  
Contractile State ◽  
Wet Weight ◽  
Near Term

Release of prostaglandin E2 (PGE2) was studied in isolated ductus arteriosus preparations from immature (103 or 104 days gestation; term, 147 days) and near-term fetal lambs. Mature preparations produced measurable amounts of the compound in most cases and the release rate was 19 ± 2 pg/(100 mg wet weight∙min) at a [Formula: see text] of 3–8 Torr (1 Torr = 133.3 Pa). PGE2 release increased with the [Formula: see text] of the medium, peak values (about 125 pg/(100 mg∙min)) being attained at 106–276 Torr when the oxygen-induced contraction was still submaximal. Experiments in which tissues were either contracted with excess potassium or relaxed with CO proved that PGE2 formation is independent from the contractile state. PGE2 was also released from ductus preparations lacking the adventitia, the intima, or both; however, release values were maximal when the adventitia was preserved. The magnitude of the intrinsic tone in these stripped preparations was inversely related to the rate of PGE2 formation. Reduced glutathione increased PGE2 release from the mature ductus, whole or stripped, and also relaxed hypoxic preparations; both effects were reversed by concomitant treatment with indomethacin. PGE2 synthesis tended to be greater in the immature than the mature ductus, maximal values (115 ± 27 pg/(100 mg∙min)) being observed at 6–8 Torr. We conclude that the ductus arteriosus is endowed with an enzyme system for the synthesis of PGE2 whose function accords with an effector role of the compound in the regulation of tone. These findings, together with the potent relaxation exerted by PGE2 at low [Formula: see text], indicate that the locally generated prostaglandin is well suited for keeping the ductus patent in the fetus.

In Vivo Imaging Of Plant Oxygen Levels

2021 ◽  
Author(s):  
Daan Adriaan Weits
Keyword(s):  
Anaerobic Fermentation ◽  
Critical Role ◽  
Model Organisms ◽  
Cellular Respiration ◽  
Oxygen Levels ◽  
Oxygen Gradients ◽  
Human Pathology ◽  
Oxygen Concentrations

Abstract Oxygen is essential for multicellular aerobic life due to its central role in energy metabolism. The availability of oxygen can drop below the level to sustain oxidative phosphorylation when plants are flooded, posing a severe threat to survival. However, under non-stressful conditions, the internal oxygen concentrations of most plant tissue is not in equilibrium with the environment, which is attributed to cellular respiration and diffusion constrains imposed by O2 barriers and bulky tissue. This is exemplified by the observations of steep oxygen gradients in roots, fruits, tubers, anthers and meristems. In order to adapt to a varying availability of oxygen, plants sense O2 via the conditional proteolysis of transcriptional regulators. This mechanism acts to switch oxidative metabolism to anaerobic fermentation, but it was also shown to play a role in plant development and pathogen defense. To investigate how dynamic and spatial distribution of O2 impacts on these processes, accurate mapping of its concentration in plants is essential. Physical oxygen sensors have been employed for decades to profile internal oxygen concentrations in plants, while genetically encoded oxygen biosensors have only recently started to see use. Driven by the critical role of hypoxia in human pathology and development, several novel oxygen sensing devices have also been characterized in cell lines and animal model organisms. This review aims to provide an overview of available oxygen biosensors, and to discuss their potential application to image oxygen levels in plants.

Modeling mechanical alternans in the beating heart: advantages of a systems-oriented approach

1987 ◽  
Vol 253 (3) ◽  
pp. H690-H698 ◽  
Author(s):  
D. Adler ◽  
Y. Mahler
Keyword(s):  
Functional Dependence ◽  
Critical Role ◽  
Beating Heart ◽  
Discrete Method ◽  
End Diastolic Volume ◽  
A Value ◽  
The Difference ◽  
Experimental Findings ◽  
The Relationship

A model employing an original discrete method is proposed to explain mechanical alternans in the beating heart. This is compared with analysis using the difference-equation method, which has been utilized in some other areas of science and found to better represent the cardiac beat-to-beat behavior. The model shows the critical role of a slope with an exact value of 2 in the functional dependence between stroke volume (SV) and the end-diastolic volume (EDV). The implications of this model with respect to the factors causing sustained mechanical alternans (SMA) in the heart are shown. A criterion for determining whether SMA is caused by variations in EDV is described. However, this possibility is ruled out on the basis of experimental findings. It is further shown that SMA caused primarily by alterations in the contractile state leads to secondary variations in EDV. In this case the model predicts that the mean slope of SV as a function of EDV, as determined by the two alternating beats, has a value of 2 and is independent of the SV-EDV relation. This prediction concerning the relationship between SV and EDV is confirmed by available experimental data. The implications and advantages of the modeling approaches are explored.

Ethanol increases uterine blood flow and fetal arterial blood oxygen tension in the near-term pregnant ewe

Alcohol ◽  
1996 ◽  
Vol 13 (3) ◽  
pp. 251-256 ◽  
Author(s):  
James D. Reynolds ◽  
Donald H. Penning ◽  
Franklin Dexter ◽  
Barry Atkins ◽  
Jim Hrdy ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Tension ◽  
Blood Oxygen ◽  
Uterine Blood Flow ◽  
Arterial Blood ◽  
Near Term ◽  
Arterial Blood Oxygen ◽  
Pregnant Ewe

scholarly journals Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents ductus arteriosus reopening

2000 ◽  
Vol 279 (1) ◽  
pp. R278-R286 ◽  
Author(s):  
Hiroki Kajino ◽  
Yao-Qi Chen ◽  
Sylvain Chemtob ◽  
Nahid Waleh ◽  
Cameron J. Koch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Concentration ◽  
Ductus Arteriosus ◽  
Tissue Hypoxia ◽  
No Production ◽  
Active Tension ◽  
Tissue Oxygen ◽  
Ambient Oxygen ◽  
Inner Vessel ◽  
Oxygen Concentrations

Regulation of ductus arteriosus (DA) tension depends on a balance between oxygen-induced constriction and PG and nitric oxide (NO)-mediated relaxation. After birth, increasing PaO2 produces DA constriction. However, as the full-term ductus constricts, it develops severe tissue hypoxia in its inner vessel wall (oxygen concentration <0.2%). We used isolated rings of fetal lamb DA to determine why the constricted ductus does not relax and reopen as it becomes hypoxic. We used a modification of the 2-(2-nitro-1 H-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) technique (Clyman RI, Chan CY, Mauray F, Chen YQ, Cox W, Seidner SR, Lord EM, Weiss H, Wale N, Evan SM, and Koch CJ. Pediatr Res 45: 19–29, 1999) to determine mean tissue oxygen concentration. A decrease in the ductus' mean tissue oxygen concentration from 1.4 to 0.1% lowers the isometric tone of the ductus by 15 ± 10% of its maximal active tension (the maximal tension that can be produced by the ductus). Although decreases in oxygen concentration diminish ductus tension, most of the vasoconstrictor tone in the ductus is independent of ambient oxygen concentration. This oxygen-independent tone is equivalent to 64 ± 10% of the maximal active tension. At mean tissue oxygen concentrations >0.2%, endogenous PGs and NO inhibit more than 40% of the active tension developed by the ductus. However, when tissue oxygen concentrations drop below 0.2%, the constitutive relaxation of the ductus by endogenous PGs and NO is lost. In the absence of PG and NO production, tension increases to a level normally observed only after treatment of the ductus with indomethacin and nitro-l-arginine methyl ester (inhibitors of PG and NO production). Therefore, under conditions of severe hypoxia (tissue oxygen concentration <0.2% oxygen), the loss of PG- and NO-mediated relaxation more than compensates for the loss of oxygen-induced tension. We hypothesize that this increased ductus tone enables the vessel to remain closed as it undergoes tissue remodeling.

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