Abstract 017: Effect of Sildenafil on Nitric Oxide-Mediated Vasodilation in the Human Placenta: an Ex-Vivo Placental Perfusion Study

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Emilie Hitzerd ◽  
Marija Glisic ◽  
Katrina M Colafella ◽  
René de Vries ◽  
Sam Schoenmakers ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Placenta ◽  
Ex Vivo ◽  
Perfusion Study ◽  
Placental Perfusion

scholarly journals Plasma proteins facilitates placental transfer of polystyrene particles

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Michael M. Gruber ◽  
Birgit Hirschmugl ◽  
Natascha Berger ◽  
Magdalena Holter ◽  
Snježana Radulović ◽  
...  
Keyword(s):  
Human Plasma ◽  
Human Placenta ◽  
Plasma Proteins ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Biological Fluids ◽  
Protein Corona ◽  
Human Albumin ◽  
Placental Perfusion ◽  
The Impact

Abstract Background Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

Transfer and Effect of Endothelin Receptor Antagonists in the Human Placenta: an Ex Vivo Perfusion Study of the Isolated Cotyledon

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e53
Author(s):  
Emilie Hitzerd ◽  
Rugina I. Neuman ◽  
Michelle Broekhuizen ◽  
Sinno H.P. Simons ◽  
Sam Schoenmakers ◽  
...  
Keyword(s):  
Human Placenta ◽  
Ex Vivo ◽  
Endothelin Receptor Antagonists ◽  
Endothelin Receptor ◽  
Receptor Antagonists ◽  
Perfusion Study ◽  
Ex Vivo Perfusion

scholarly journals Transplacental pharmacokinetic model of digoxin based on ex vivo human placental perfusion study

2021 ◽  
pp. DMD-AR-2021-000648
Author(s):  
Ken Kurosawa ◽  
Saki Noguchi ◽  
Tomohiro Nishimura ◽  
Masatoshi Tomi ◽  
Koji Chiba
Keyword(s):  
Pharmacokinetic Model ◽  
Ex Vivo ◽  
Perfusion Study ◽  
Placental Perfusion

Mechanism of clearance and transfer of dipeptides by perfused human placenta

1996 ◽  
Vol 271 (3) ◽  
pp. E535-E540 ◽  
Author(s):  
S. A. Adibi ◽  
S. Schenker ◽  
E. Morse
Keyword(s):  
Parenteral Nutrition ◽  
Human Placenta ◽  
Brush Border Membrane ◽  
Membrane Vesicles ◽  
Small Concentration ◽  
Complete Disappearance ◽  
Perfusion Study ◽  
Placental Perfusion ◽  
Transcellular Transport ◽  
Stable Source

Glycylglutamine (Gly-Gln) is stable source of glutamine for parenteral nutrition. In the present study we have investigated whether this dipeptide is transferred intact across the human placenta. Although after 90 min of placental perfusion there was almost complete disappearance of Gly-Gln (100 microM) from the maternal compartment, only a small concentration of this dipeptide (< 6 microM) appeared in the fetal compartment. To investigate whether this transfer was due to transcellular transport, brush-border membrane vesicles of the human placenta were probed with [3H]Gly-Gln, which showed no uptake. To investigate whether hydrolysis was the mechanism of disappearance of Gly-Gln, the perfusion study was repeated with glycylsarcosine (Gly-Sar), which is resistant to hydrolysis. In sharp contrast to Gly-Gln, after 90 min of perfusion nearly 80% of Gly-Sar remained in the perfusate (half-life of 24 vs. 235 min). The rest of the Gly-Sar was recovered intact in the fetal compartment. The addition of Gly-Gln to the maternal compartment increased the accumulation of glycine, but not glutamine, in both the maternal and fetal compartments. In conclusion, our data suggest that 1) the mechanism of clearance of Gly-Gln by perfused human placenta is largely hydrolysis, whereas that of Gly-Sar is largely passive diffusion, and 2) the placenta has a greater preference for glutamine than for glycine.

scholarly journals Real time measurement of nitric oxide produced ex vivo by luminol-H2O2 chemiluminescence method.

1993 ◽  
Vol 268 (31) ◽  
pp. 23106-23110
Author(s):  
K Kikuchi ◽  
T Nagano ◽  
H Hayakawa ◽  
Y Hirata ◽  
M Hirobe
Keyword(s):  
Nitric Oxide ◽  
Real Time ◽  
Ex Vivo ◽  
Time Measurement ◽  
Chemiluminescence Method ◽  
Real Time Measurement

Nitric oxide synthase from human placenta

Placenta ◽  
1997 ◽  
Vol 18 ◽  
pp. 141-153 ◽  
Author(s):  
Sachio Iida ◽  
Hiroyuki Ohsawa ◽  
Hiroaki Soma ◽  
Toshio Hata ◽  
Yukiko Kurashima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Human Placenta ◽  
Oxide Synthase

Homocyst(e)ine impairs endocardial endothelial function

1999 ◽  
Vol 77 (12) ◽  
pp. 950-957 ◽  
Author(s):  
Suresh C Tyagi ◽  
Lane M Smiley ◽  
Vibhas S Mujumdar
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Cardiac Function ◽  
Vascular Function ◽  
Ex Vivo ◽  
Cardiac Contraction ◽  
Normal Male ◽  
Wistar Kyoto ◽  
Endocardial Endothelium ◽  
Endothelial Nitric Oxide

Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 106 and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (p < 0.005, compared with intact endothelium) and equal to the response to ET and AII. To determine the physiological significance of ET, AII, homocyst(e)ine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10-10 M) or ET (10-13 M) and then treated with homocyst(e)ine (10-8 M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10-10 M AII or 10-13 M ET, the cardiac contraction to homocyst(e)ine (10-8 M) was significantly enhanced (p < 0.01, compared with without pretreatment) and further increased in the endocardium without endothelium. The pretreatment of cardiac ring with the inhibitor of nitric oxide, Nω-nitro-L-arginine methyl ester (L-NAME), increased contractile response to homocyst(e)ine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.Key words: endocardial remodeling, homocyst(e)ine, contraction, endothelin, angiotensin, endothelial-derived relaxing factor (EDRF), Nω-nitro-L-arginine methyl ester (L-NAME), endothelial dysfunction, ex vivo cardiac function, heart failure.

Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone

2004 ◽  
Vol 286 (1) ◽  
pp. H230-H239 ◽  
Author(s):  
Yuan-Lin Dong ◽  
Sujatha Vegiraju ◽  
Madhu Chauhan ◽  
Pandu R. R. Gangula ◽  
Gary D. V. Hankins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Placenta ◽  
Vascular Tone ◽  
Umbilical Artery ◽  
Force Measurement ◽  
Isometric Force ◽  
Calcitonin Gene Related Peptide ◽  
Immunofluorescent Staining ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP8–37), ATP-sensitive potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor ( Nω-nitro-l-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of KATP channels, cAMP, and a nitric oxide pathway.

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