The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women

2004 ◽  
Vol 286 (6) ◽  
pp. R1102-R1109 ◽  
Author(s):  
Leonid Luksha ◽  
Henry Nisell ◽  
Karolina Kublickiene
Keyword(s):  
Gap Junctions ◽  
Pregnant Women ◽  
Subcutaneous Fat ◽  
Specific Inhibitor ◽  
Normal Pregnancy ◽  
Induced Responses ◽  
Response Curves ◽  
Small Arteries ◽  
Isolated Arteries ◽  
Cytochrome P 450

We studied the importance of endothelium-derived hyperpolarizing factor (EDHF) vs. nitric oxide (NO) and prostacyclin (PGI2) in bradykinin (BK)-induced relaxation in isolated small subcutaneous arteries from normal pregnant women. We also explored the contribution of cytochrome P-450 (CYP450) product of arachidonic acid (AA) metabolism, hydrogen peroxide (H2O2), and gap junctions that have been suggested to be involved in EDHF-mediated responses. Isolated arteries obtained from subcutaneous fat biopsies of normal pregnant women ( n = 30) undergoing planned cesarean section were mounted in a wire-myography system. In norepinephrine-constricted vessels, incubation with NG-nitro-l-arginine methyl ester (l-NAME) resulted in a significant reduction in relaxation to BK. Simultaneous incubation with l-NAME and indomethacin failed to modify this response further. BK-mediated dilatation in the presence of K+-modified solution was decreased to similar level as obtained after incubation with l-NAME. Incubation with l-NAME abolished BK-induced responses in K+-modified solution. Sulfaphenazole, a specific inhibitor of CYP450 epoxygenase, and catalase (an enzyme that decomposes H2O2) did not affect the EDHF-mediated relaxation because concentration-response curves to BK were similar in arteries after incubation with l-NAME vs. l-NAME + sulfaphenazole and l-NAME + catalase. The inhibitor of gap junctions, 18α-glycyrrhetinic acid, significantly reduced BK-mediated relaxation both without and with incubation with l-NAME. We found that both NO and EDHF, but not PGI2, are involved in the endothelium-dependent dilatation to BK. BK-induced relaxation is almost equally mediated by NO and EDHF. CYP450 epoxygenase metabolites of AA or H2O2 do not account for EDHF-mediated response; however, gap junctions are involved in the EDHF-mediated responses to BK in subcutaneous small arteries in normal pregnancy.

Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia

2002 ◽  
Vol 103 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Louise C. KENNY ◽  
Philip N. BAKER ◽  
David A. KENDALL ◽  
Michael D. RANDALL ◽  
William R. DUNN
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Pregnant Women ◽  
Cell Function ◽  
Normal Pregnancy ◽  
Induced Responses ◽  
Endothelial Cell Function ◽  
Small Arteries ◽  
Nos Inhibitor ◽  
Oxide Synthase

Pre-eclampsia is a pregnancy-specific disorder associated with hypertension and proteinuria, characterized by alterations in endothelial cell function. In the present study we have compared responses to the endothelium-dependent vasodilator, bradykinin, in small myometrial arteries from normal pregnant and non-pregnant women and women with pre-eclampsia, in order to assess the relative contributions of nitric oxide, endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in mediating endothelium-dependent vasodilatation. Bradykinin-induced concentration-dependent relaxation in arteries isolated from the three subject groups did not differ with regard to sensitivity or maximum response. Responses to bradykinin in all three groups were unaffected by cyclo-oxygenase inhibition alone, and were similarly unaffected by partial depolarization. The nitric oxide synthase (NOS) inhibitor, N-nitro-l-arginine methyl ester, significantly attenuated the responses to bradykinin in arteries from non-pregnant women and almost abolished responses in arteries from women with pre-eclampsia. However, in arteries from normal pregnant women, bradykinin-induced responses were maintained in the presence of NOS inhibition. Inhibition of NOS combined with partial depolarization abolished responses to bradykinin in these vessels. These results support the suggestion that, in the absence of NO, an EDHF can mediate vasodilator responses to bradykinin during normal pregnancy, an effect not apparent in arteries from non-pregnant women or women with pre-eclampsia. The up-regulation of EDHF-type function may represent a vascular adaptation to normal pregnancy that is absent in pre-eclampsia, and this might contribute to the clinical features of the disease.

scholarly journals Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites

2008 ◽  
Vol 294 (2) ◽  
pp. R510-R519 ◽  
Author(s):  
Leanid Luksha ◽  
Henry Nisell ◽  
Natallia Luksha ◽  
Marius Kublickas ◽  
Kjell Hultenby ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Subcutaneous Fat ◽  
Normal Pregnancy ◽  
Transmission Electron ◽  
Main Pathway ◽  
Before And After ◽  
Group 2 ◽  
Cytochrome P 450 ◽  
Group 1

We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries (≈200 μm) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE ( n = 13) and NP ( n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced ( P < 0.05). All women within the PE group were divided into two subgroups: with more ( group 1) or less ( group 2) than 50% reduction of EDHF-typed responses after 18-α-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H2O2 and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H2O2 or cytochrome P-450 epoxygenase metabolites of AA.

scholarly journals The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women

2002 ◽  
Vol 136 (8) ◽  
pp. 1085-1088 ◽  
Author(s):  
Louise C Kenny ◽  
Philip N Baker ◽  
David A Kendall ◽  
Michael D Randall ◽  
William R Dunn
Keyword(s):  
Gap Junctions ◽  
Pregnant Women ◽  
Small Arteries

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

2006 ◽  
Vol 290 (5) ◽  
pp. H1969-H1975 ◽  
Author(s):  
Maria Natalia Cruz ◽  
Leonid Luksha ◽  
Henareh Logman ◽  
Lucilla Poston ◽  
Stefan Agewall ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ex Vivo ◽  
Subcutaneous Fat ◽  
Estrogen Receptor Α ◽  
Response Curves ◽  
Small Arteries ◽  
Before And After ◽  
Established Coronary Heart Disease ◽  
Normal Men

The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-α (ERα) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERβ agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERα agonist) were determined. These were compared with responses to reference compound 17β-estradiol (17β-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nω-nitro-l-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17β-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17β-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.

Connexin 43 mediates endothelium-derived hyperpolarizing factor-induced vasodilatation in subcutaneous resistance arteries from healthy pregnant women

2007 ◽  
Vol 292 (2) ◽  
pp. H1026-H1032 ◽  
Author(s):  
Ninian N. Lang ◽  
Leonid Luksha ◽  
David E. Newby ◽  
Karolina Kublickiene
Keyword(s):  
Gap Junctions ◽  
Pregnant Women ◽  
Connexin 43 ◽  
Subcutaneous Fat ◽  
Cyclooxygenase Inhibitors ◽  
Elective Cesarean Section ◽  
Resistance Arteries ◽  
Cx43 Expression ◽  
Elective Cesarean ◽  
Oxide Synthase

The role of gap junctions in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation of human arteries was assessed using connexin mimetic peptides (CMPs) designated 37,43Gap27, 40Gap27, and 43Gap26 according to homology with the major vascular connexins (Cx37, Cx40, and Cx43). Resistance arteries were obtained from subcutaneous fat biopsies of healthy pregnant women undergoing elective cesarean section. Endothelium-dependent vasodilatation to bradykinin (BK) was assessed using wire myography. Nω-nitro-l-arginine methyl ester (l-NAME) and indomethacin (nitric oxide synthase and cyclooxygenase inhibitors, respectively) attenuated maximal relaxation to BK (Rmax) by ∼50%. Coincubation with l-NAME, indomethacin, and the combined CMPs (37,43Gap27, 40Gap27, and 43Gap26) almost abolished relaxation to BK (Rmax = 12.2 ± 3.7%). In arteries incubated with l-NAME and indomethacin, the addition of either 37,43Gap27 or 40Gap27 had no significant effect on Rmax, whereas 43Gap26 caused marked inhibition (Rmax = 21 ± 6.4%, P = 0.005 vs. l-NAME plus indomethacin alone) that was similar to that of the triple combination. Endothelium-independent vasorelaxation was unaffected by CMPs, l-NAME, or indomethacin. Immunohistochemistry demonstrated Cx37, Cx40, and Cx43 expression in the endothelium and vascular smooth muscle. In pregnant women, EDHF-mediated vasorelaxation of subcutaneous resistance arteries is dependent on Cx43 and gap junctions.

Pathological features of the sequence in pregnant women with delayed fetal growth

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  
Keyword(s):  
Pregnant Women ◽  
Intrauterine Growth Restriction ◽  
Normal Development ◽  
Intrauterine Infection ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Infection And Inflammation

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.

scholarly journals Group B streptococcus colonization of pregnant women and their children observed on obstetric and neonatal wards of the University Hospital in Krakow, Poland

2009 ◽  
Vol 58 (2) ◽  
pp. 228-233 ◽  
Author(s):  
Magdalena Strus ◽  
Dorota Pawlik ◽  
Monika Brzychczy-Włoch ◽  
Tomasz Gosiewski ◽  
Krzysztof Rytlewski ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Molecular Typing ◽  
Horizontal Transmission ◽  
Group B Streptococcus ◽  
Normal Pregnancy ◽  
University Hospital ◽  
Hospital Environment ◽  
Eastern Region ◽  
Group B ◽  
Complicated Pregnancy

The study was arranged to assess the actual rates of colonization of pregnant women and their children with group B streptococcus (GBS) in a Polish university hospital. Resistance of these cocci to macrolides and clindamycin was also tested and routes of transmission of GBS were followed in some cases using molecular typing. Colonization with GBS was checked in 340 pregnant women living in the south-eastern region of Poland (Małopolska) in the years 2004–2006. Women with a complicated pregnancy were more often colonized than those with a normal pregnancy (20.0 % versus 17.2 %). Moreover, women with a complicated pregnancy were twice as often colonized with GBS strains with the MLSB phenotype indicating resistance to macrolides and clindamycin. Regarding neonatal colonization by GBS, we found that neonates born from the colonized mothers with a complicated pregnancy were more often colonized with GBS than those from the mothers with a normal pregnancy (35 % versus 26.7 %). By molecular typing of the GBS strains isolated from mothers and their newborns we have been able to suggest the possibility of horizontal transmission of the strains from the hospital environment to newborns. Our results clearly indicate that rates of GBS colonization among pregnant women and neonates in a Polish university hospital have reached levels comparable to those reported in other European clinical centres.

Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies

1996 ◽  
Vol 134 (1) ◽  
pp. 84-86 ◽  
Author(s):  
Judith Roberts ◽  
Carol Jenkins ◽  
Rhoda Wilson ◽  
Charles Pearson ◽  
Ian A Franklin ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Spontaneous Abortion ◽  
Recurrent Miscarriage ◽  
Previous History ◽  
Cell Subset ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Anticardiolipin Antibodies ◽  
Royal Infirmary ◽  
Thyroid Antibodies

Roberts J. Jenkins C, Wilson R, Pearson C, Franklin IA, MacLean MA, McKillop JH, Walker JJ. Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies. Eur J Endocrinol 1996;134:84–6. ISSN 0804–4643 The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 ± 0.3 vs 0.5 ± 0.1 vs 1.1 ± 0.3 × 108/l: p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage. R Wilson, Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK

scholarly journals Learn It, Buy It, Work It: Intensive Pregnancy on Instagram

2017 ◽  
Vol 3 (1) ◽  
pp. 205630511668510 ◽  
Author(s):  
Katrin Tiidenberg ◽  
Nancy K. Baym
Keyword(s):  
Pregnant Woman ◽  
Pregnant Women ◽  
Normal Pregnancy ◽  
Authoritative Knowledge ◽  
Consumer Identity ◽  
Discursive Power

This article analyzes how pregnant women perform their pregnancies on Instagram. We ask whether they rely on and reproduce pre-existing discourses aimed at morally regulating pregnancy, or reject them and construct their own alternatives. Pregnancy today is highly visible, intensely surveilled, marketed as a consumer identity, and feverishly stalked in its celebrity manifestations. This propagates narrow visions of what a “normal” pregnancy or “normal” pregnant woman should be like. We argue that pregnant women on Instagram do pregnancy via three overlapping and complimentary discourses of “learn it,” “buy it,” and “work it.” Together these form the current authoritative knowledge of pregnancy we call “intensive pregnancy” as performed on Instagram. Concurrently, this article highlights how the combined discursive power of hashtags, images, and captions may influence and enforce discursive hegemonies.

scholarly journals Serum pituitary antibodies in normal pregnancy and in patients with postpartum thyroiditis: a nested case–control study

2008 ◽  
Vol 159 (6) ◽  
pp. 805-809 ◽  
Author(s):  
Luca Manetti ◽  
Arthur B Parkes ◽  
Isabella Lupi ◽  
Graziano Di Cianni ◽  
Fausto Bogazzi ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Case Control Study ◽  
Normal Pregnancy ◽  
Case Control ◽  
Free Triiodothyronine ◽  
Function Impairment ◽  
Pituitary Antibodies ◽  
Nested Case Control ◽  
Control Study ◽  
Antithyroid Autoantibodies

ObjectivesThe aim of this study was to evaluate antipituitary antibody (APA) prevalence in a series of patients with postpartum thyroiditis (PPT) during pregnancy and in the postpartum.DesignWe conducted a nested case–control study on consecutive PPT and normal pregnant women at the Centre for Endocrine and Diabetes Sciences in Cardiff and at the Department of Endocrinology in Pisa.MethodsWe enrolled 30 women with PPT: 17 were hypothyroid (Hypo), 7 with hyperthyroidism (Hyper) and 6 with a transient hyperthyroidism followed by hypothyroidism (Biphasic). Twenty-one healthy pregnant women served as controls. APA (measured using indirect immunofluorescence), free thyroxine, free triiodothyronine, TSH, antithyroid autoantibodies, and thyroid ultrasound were performed during pregnancy and postpartum. The stored sera have been sent to Pisa, where serum APA, IGF1, and cortisol were measured.ResultsAPA were found in 8 out of the 30 PPT patients (26.7%) and in one normal pregnancy (4.7%, P=0.063). Three out of the seventeen Hypo with PPT (17.6%), three out of the seven Hyper PPT (42.8%), and two out of the six Biphasic PPT (33.3%) were positive for APA. APA prevalence was not significantly different in the PPT subgroups (P=0.453). With one exception, APA all increased in the postpartum period (87.5%, P<0.016). Basal serum IGF1 and cortisol were in the normal range with the exception of two patients with positive APA who presented low serum IGF1 levels (36 and 45 ng/ml).ConclusionsAPA are frequently present in the postpartum period in patients affected by PPT. Further studies are necessary to evaluate whether APA in PPT patients are associated with pituitary function impairment.

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