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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homogenized first trimester human placenta exhibits both Ca(2+)-dependent (90-95 per cent) and Ca(2+)-independent (5-10 per cent) nitric oxide (NO)-synthesizing activities. Addition of tetrahydrobiopterin (BH4) to homogenates containing Ca2+ in maximally activating concentrations (> 0.5 microM) results in a further 2-2.5-fold activation of NO synthesis, with half-maximal stimulation observed at 26 +/- 8.2 microM BH4 (mean +/- SEM, n = 4). Chelation of Ca2+ in the medium abolishes the stimulatory effect, indicating that only a Ca2(+)-dependent NO-synthase (NOS) isoform is activated by BH4. Based on our previous findings, we suggest that this isoform is the endothelial or Type III NOS. Importantly, BH4 has no significant effect on the Ca2(+)-dependency of NOS activity, the apparent Km values for Ca2+ are comparable in the absence (1.8 +/- 0.4 microM, mean +/- SEM, n = 6) or presence (2.5 +/- 0.6 microM, mean +/- SEM, n = 6) of 50 microM BH4. The BH4 content of these placentae is 207.4 +/- 86.7 pmol/g wet tissue (mean +/- s.d., n = 9), therefore, BH4 added to the homogenate does not simply restore the concentrations that occur endogenously. The results provide the first evidence that in the early human placenta, a constitutively expressed CA 2(+)-dependent NOS isoform is stimulated by exogenous BH4, raising the possibility that BH4 is an important regulator of NOS activity in this tissue. This novel aspect of the NO-generating pathway may have implications in the aetiology and treatment of pregnancy-induced hypertension and pre-eclampsia.
Placenta 1996 Jan
PMID:Calcium-dependent nitric oxide synthesis is potently stimulated by tetrahydrobiopterin in human primordial placenta. 871 Aug 15

The recent discovery of a local renin-angiotensin system in trophoblastic tissues has raised many questions regarding its role in the physiology of normal gestation and its implications in the pathophysiology of hypertension during pregnancy. In this article, the authors first review the most interesting aspects of the chorioplacental renin-angiotensin system, dwelling on the tissue distribution of angiotensin II and its receptor subtypes in the placenta and fetal membranes of different species. The relationship between angiotensin II and other locally synthesized chorioplacental substances is also analysed and the therapeutic implications of phenomena observed in pregnancy-associated hypertension are discussed.
Placenta
PMID:Angiotensin II and its different receptor subtypes in placenta and fetal membranes. 873 Aug 80

The aim of this study was to examine whether differences in placental angiotensinase A (glutamyl aminopeptidase, EC 3.4.11.7) activities occurred in hypertensive complications of pregnancy compared with uncomplicated pregnancies. Biochemical and semiquantitative histochemical methods were used and compared for their applicability. Angiotensinase A activity was detected using L-alpha glutamyl-4-methoxy-2-naphthylamide (alpha-Glu-MNA) as substrate and Fast Blue B salt for simultaneous azo-coupling in cryostat sections of placental tissue samples from 32 patients with pre-eclampsia, 11 patients with pregnancy-induced hypertension and 44 participants with uncomplicated pregnancies. The graduated intensity of reaction product in the villous trophoblast and in fetal blood vessels was evaluated semiquantitatively in a double-blind study by light microscopy (semiquantitative score method). Score levels were related to relative frequencies of hypertensive disorders (proportional odds model) and correlated to the severity of gestational hypertension (Spearman's rank correlation). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements under the same substrate and buffer conditions as in enzyme histochemistry. Enhanced villous trophoblastic angiotensinase A activity was significantly associated with an increased frequency of pre-eclampsia in pregnant women (cumulative odds ratio x 0(1) 6.37; P < 0.001) and showed significant correlations with the severity of gestational hypertensive disorders, represented by systolic (r = 0.31; P < 0.05) and diastolic (r = 0.34; P < 0.05 blood pressure and by concomitant proteinuria (r = 044; P < 0.01). Histochemical evaluation of fetal blood vessels and biochemical measurements revealed no statistically significant results. In conclusion this study demonstrates for the first time that increased villous trophoblastic angiotensinase A activity indicates an increased likelihood of the presence of pre-eclampsia and the severity of hypertensive disorders in pregnancy.
Placenta
PMID:Histochemical evaluation of placental angiotensinase A in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational proteinuric hypertension. 873 Aug 85

Hypertension is strongly predicted by a low birthweight:placental weight ratio. Two independent models have been described to explain this association; less than optimal maternal protein nutrition leading to fetal undernutrition, or glucocorticoid excess. Pregnant rats were fed diets containing 18 per cent casein (control) or 9 per cent casein, balanced for energy. On day 20 of gestation the pregnancies were terminated and placentae collected for determination of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity. Placental 11 beta HSD normally protects the fetus from the effects of maternal glucocorticoids. Activity was specifically attenuated by mild protein restriction (33 per cent in activity), whilst activities of glucocorticoid-insensitive control enzymes were unchanged and glucocorticoid-inducible glutamine synthetase activity was increased (27 per cent), relative to activity in placentae from control animals. The nutritional manipulation during pregnancy significantly increased systolic blood pressure (17 mmHg) in the resulting offspring in early adulthood. A possible common pathway whereby maternal environmental factors may influence fetal and placental growth and programme disease is inferred.
Placenta
PMID:Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. 873 Aug 87

Villous trophoblasts isolated from term placentae of normal pregnancies, and pregnancies complicated by chronic hypertension or pre-eclampsia, were examined over 7 days in primary culture. Low levels of prostaglandin E2 and prostacyclin (measured as 6-keto prostaglandin Fl alpha) were secreted by trophoblast cells from all three clinical groups. Secretion was maximal at day 1 and decreased exponentially thereafter. Thromboxane secretion also fell sequentially from day 1. Thromboxane secretion by pre-eclamptic trophoblasts was three to four times that of cells from normal or chronically hypertensive subjects. Prostanoid secretion by isolated cultured cytotrophoblasts was not dependent on aggregation or morphological alteration, nor related to changes in progesterone or human chorionic gonadotrophin production. Because the local maternal circulation is exposed to substances secreted by this cell population, thromboxane could be the trigger for vasoconstriction and coagulation found within the maternal uteroplacental circulation in pre-eclampsia.
Placenta 1996 Sep
PMID:In-vitro secretion of prostanoids by placental villous cytotrophoblasts in pre-eclampsia. 889 69

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.
Placenta 1998 Jan
PMID:Clinical correlations of patterns of placental pathology in preterm pre-eclampsia. 948 87

To identify tumour necrosis factor (TNF)-alpha immunopositive cells, third trimester human placental bed biopsies were selected from nine normotensive control women, 16 severely pre-eclamptic patients and seven patients with pre-existing hypertension with superimposed pre-eclampsia. In addition, five first and early second trimester specimens were included in the study. Immunostaining was performed with a mouse IgG1 monoclonal antibody (J1D9) reactive specifically with human TNF-alpha (1:300 ascitic fluid), using a biotin-streptavidin-peroxidase technique. Variable staining of stromal cells was noted in all biopsies. Specimens of early pregnancy showed marked immunostaining for TNF-alpha on proliferating tips of anchoring villi, invasive interstitial cytotrophoblast (but not the multinuclear giant cells), and endovascular trophoblast invading the spiral arteries. At term, weak staining was found in trophoblast incorporated within spiral artery walls. In biopsies from pre-eclamptic patients, spiral arteries without physiological change showed very little staining except in atherotic vessels where the infiltrated lipophages often showed intense immunolabelling. The marked presence of TNF-alpha in extravillous cytotrophoblast of young specimens is suggestive of a role in early invasion. Immunostaining of foam cells in non-invaded spiral arteries in pre-eclampsia at or near-term indicates a potential role of this cytokine in the development of atherotic lesions.
Placenta 1998 May
PMID:Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental bed of normotensive and hypertensive human pregnancies. 963 18

Pre-eclampsia is a hypertensive disorder of human pregnancy that is a leading cause of premature delivery and fetal growth retardation. It is characterized by hypertension, reduced uteroplacental blood flow, proteinuria and oedema. Pre-eclampsia is associated with increased lipid peroxidation in the maternal circulation and in the placenta. Mitochondria are sources of oxygen radicals and are enriched with polyunsaturated fatty acids that are susceptible to peroxidation. Therefore, the mitochondria could be an important source of oxidative stress and lipid peroxidation. To study this, the level of lipid peroxidation in the mitochondrial fraction of placentae obtained from normally pregnant women (n=8) and women with pre-eclampsia (n=8) was examined. Placental tissues were homogenized and the mitochondrial fraction was isolated by ultracentrifugation. Mitochondrial lipid peroxides were estimated by malondialdehyde (MDA). NADPH and Fe++ were used to stimulate lipid peroxidation. Superoxide dismutase (SOD) was used to inhibit superoxide radicals and mannitol to inhibit hydroxyl radicals. The following results were found: (1) MDA levels were significantly greater in the mitochondrial fraction isolated from pre-eclamptic placentae than from normal placentae (27.4+/-3.0 versus 17.0+/-1.8 nmol/g tissue, mean+/-s.e., P<0.05); (2) the oxidative potential of the pre-eclamptic mitochondrial fraction was also higher than normal as evidenced by the significantly greater stimulation of lipid peroxidation by NADPH and Fe+ + (248+/-25 versus 164+/-35 nmol/g, P<0.05); (3) superoxide dismutase, but not mannitol, attenuated the lipid peroxidation induced by NADPH and Fe+ + demonstrating that superoxide is the radical responsible for mitochondrial lipid peroxidation in this system; and (4) the amount of mitochondrial protein was 47 per cent greater and the activity of the mitochondrial enzyme, citrate synthase, was 56 per cent greater in the pre-eclamptic placentae indicating an increase in the amount of mitochondria in the pre-eclamptic placentae. It is concluded that: (1) mitochondrial lipid peroxidation is increased in pre-eclampsia; (2) the amount of placental mitochondria is increased in pre-eclampsia; (3) placental mitochondria contribute to the abnormal increase in lipid peroxidation that occurs in pre-eclamptic placentae by both an increase in their amount and an increase in their susceptibility to oxidation; and (4) mitochondrial generation of superoxide could be an important source of oxidative stress in pre-eclampsia.
Placenta 1998 Nov
PMID:Placental mitochondria as a source of oxidative stress in pre-eclampsia. 985 61

Maternal hypertension, vasoconstriction and placental insufficiency are features of pre-eclampsia. Alterations in calcium homeostasis and in the production of calciotropic hormones and vasoactive agents have also been described in association with pre-eclampsia. Parathyroid hormone-related protein (PTHrP) is abundantly expressed in intrauterine tissues during normal pregnancy and has roles in fetal growth and calcium homeostasis, placental calcium transport and vascular tone regulation. Intrauterine PTHrP mRNA expression and tissue PTHrP content were determined by Northern blot analysis and radio-immunoassay, respectively, in preterm and term pre-eclamptic women. PTHrP mRNA expression and PTHrP content in placenta, amnion over placenta, reflected amnion and choriodecidua from preterm pre-eclamptic women (n=8-10) were not different from preterm controls (n= 10-12). PTHrP mRNA expression and content in amnion over placenta and reflected amnion were significantly greater in term compared to preterm pre-eclamptics (P<0.05). PTHrP mRNA expression was significantly lower in choriodecidua from term pre-eclamptic women (n=8) compared to term controls (n=28, P<0.05), but was not different in placenta or amnion. PTHrP content was not altered in term pre-eclamptic women (n=8) compared to controls (n=25) for any tissue. In summary, PTHrP expression in placenta and amnion was not increased in pre-eclamptic women in association with maternal hypertension, placental insufficiency and vasoconstriction. PTHrP mRNA expression was decreased in choriodecidua in association with term but not preterm pre-eclampsia, however, levels of the protein were not decreased. The data suggest that PTHrP is not involved in the placental pathophysiology of pre-eclampsia in late gestation.
Placenta 1998 Nov
PMID:Intrauterine expression of parathyroid hormone-related protein in normal and pre-eclamptic pregnancies. 985 63

During early pregnancy, placentation occurs in a relatively hypoxic environment which is essential for appropriate embryonic development. Intervillous blood flow increases at around 10-12 weeks of gestation and results in exposure of the trophoblast to increased oxygen tension (PO2). Prior to this time, low oxygen appears to prevent trophoblast differentiation towards an invasive phenotype. In other mammalian systems, oxygen tension effects are mediated by hypoxia inducible factor-1 (HIF-1). We found that the ontogeny of HIF-1alpha subunit expression during the first trimester of gestation parallels that of transforming growth factor-beta3 (TGFbeta3), an inhibitor of early trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls at around 10 weeks of gestation when placental PO2 levels are believed to increase. Antisense-induced inhibition of HIF-1alpha inhibited the expression of TGFbeta3, and stimulated extravillous trophoblast (EVT) outgrowth and invasion. Of clinical significance we found that TGFbeta3 expression was increased in pre-eclamptic placentae when compared to age-matched controls. Significantly, inhibition of TGFbeta3 by antisense oligonucleotides or antibodies restored the invasive capability to the trophoblast cells in pre-eclamptic explants. We speculate that if oxygen tension fails to increase, or trophoblasts do not detect this increase, HIF-1alpha and TGFbeta3 expression remain high, resulting in shallow trophoblast invasion and predisposing the pregnancy to pre-eclampsia. Effective fetal-maternal interactions during early placentation are critical for a successful pregnancy. Optimal placental perfusion requires the controlled invasion of trophoblast cells deep into the decidua to the spiral arteries. Trophoblast stem cells, also referred to as cytotrophoblast cells, reside in chorionic villi of two types, floating and anchoring villi. Floating villi, which represent the vast majority of chorionic villi, are bathed in maternal blood and primarily perform gas and nutrient exchange for the developing embryo. During early placentation, cytotrophoblast cells in the floating villi proliferate and differentiate by fusing to form the multinucleate syncytiotrophoblast layer. Cytotrophoblast cells in anchoring villi either fuse to form the syncytiotrophoblast layer, or break through the syncytium at selected sites and form multilayered columns of non-polarized extravillous trophoblast cells, which physically connect the embryo to the uterine wall (Figure 1). The extravillous trophoblast cells invade into the uterine wall as far as the first third of the myometrium and its associated spiral arteries, where they disrupt the endothelium and the smooth muscle layer and replace the vascular wall. This results in the conversion of the narrow calibre arteries into distended uteroplacental arteries, thereby increasing blood flow to the placenta and allowing an adequate supply of oxygen and nutrients to the growing fetus. The invasive activity of the extravillous trophoblast cells is at a maximum during the first trimester of gestation, peaking at around 10-12 weeks and declining thereafter. Insufficient invasion contributes to the development of pre-eclampsia, which often results in fetal intrauterine growth restriction, maternal hypertension and proteinuria. In contrast, unrestricted invasion is associated with premalignant conditions, such as invasive mole, and with malignant choriocarcinoma. Invading trophoblast cells undergo striking and rapid changes in cellular functions that are temporally and spatially regulated along the invasive pathway (Figure 1) (Cross, Werb and Fisher, 1994. The formation of the anchoring villi is accompanied by changes in synthesis and degradation of extracellular matrix proteins and their receptors, and changes in the spatial distribution of extracellular matrix proteins, as well as changes in the expression of adhesion molecules (Damsky, Fitzgerald and
Placenta
PMID:Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. 1083 Nov 18


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