Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemorrhagic endovasculitis (HEV) is a recently described vasodestructive process within the placenta. Similarities to several forms of thrombotic microangiopathy are evident. Clinical studies have shown strong associations between HEV, still birth and intrauterine growth retardation (IUGR). Liveborn infants, with affected placentae, evaluated at the age of five, exhibit a high incidence of neurological abnormalities. HEV has been recurrent in successive pregnancies in some patients. Clinicopathological processes, which appear to be associated with HEV, include the presence of chronic villitis (VUA) and maternal hypertension. Viral- and/or Mycoplasma-type particles have been identified in a number of affected placentae examined by electron microscopy. Associated pathological events suggest an infectious aetiology possibly acting in concert with an environmental toxin. Biochemical factors and alterations of immune response within the maternal-placental-fetal unit may be involved.
Placenta
PMID:Haemorrhagic endovasculitis of the placenta: a review with clinical correlation. 354 Sep 32

An immunohistochemical method was used to locate pregnancy-associated plasma protein A (PAPP-A) in the placenta and uterus. In addition to 10 placentae and basal plates from normal pregnancies, ranging in gestational age from 37 to 40 weeks, the following specimens were studied: three uteri obtained by hysterectomy during early pregnancy; and three placentae from patients with severe hypertensive pre-eclampsia. In early gestation, PAPP-A was localized in the villous cytotrophoblastic cell layer and the endometrial glands but was not found in the villous syncytiotrophoblast, the cytotrophoblastic cell columns or the decidual cells. On histochemical examination of placentae from cases of pre-eclampsia with hypertension, an increased number of villous cytotrophoblastic cells and so-called X-cells was observed. The monospecific antiserum to PAPP-A reacted strongly and evenly with the cytoplasm of these cells. The present study strongly suggests that the active production sites of PAPP-A are the villous cytotrophoblastic cells and the X-cells.
Placenta
PMID:Immunohistochemical localization of pregnancy-associated plasma protein A (PAPP-A) in placentae from normal and pre-eclamptic pregnancies. 620 2

Approximately 6 per cent of placentae of babies admitted to a special care paediatric unit show evidence of peripheral villous stem branch oedema. In more than half of these cases there is evidence of fibrinous vasculosis (FV) in truncal veins. The affected placentae are generally thick and of small diameter, often of extrachorialis type, very congested and often cyanosed. The aetiology of the lesions is discussed with reference to abnormal fetal vascular patterns, poor perfusion, anoxia, oedema and spasm and the effect such factors may have on vessels with an irregularly distributed muscle coat and tendency to a spiral course. A small heterogeneous group with FV lesions unassociated with stem branch oedema was also identified. Chorionic vessels were more commonly involved in this group, and it would seem that, in addition to the other factors mentioned above, pressure variations may have some aetiological significance. Lesions of FV occurred mainly in mature placentae. The mothers showed a high incidence of pregnancy-induced hypertension and other complications. Fetal distress and asphyxia at birth were common. Where chorionic vessels were involved there was a high risk of intrauterine death (40 per cent) and coagulopathy among survivors (46.7 per cent). FV lesions affecting truncal vessels carried no greater risk than truncal arterial thrombotic lesions, which have been assessed in the past. In both these groups the hypoxia and intrauterine growth retardation which the babies showed are probably the most important factors, though one could postulate that their clotting mechanism was already triggered.
Placenta
PMID:Fibrinous vasculosis in the human placenta. 685 90

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.
Placenta 1995 Jul
PMID:Hypertension in pregnancy: changes in activin A maternal serum concentration. 747 15

Thromboxane has been implicated in the pathogenesis of maternal hypertension in high-risk pregnancies, but potential abnormalities in thromboxane-mediated constriction of fetoplacental vessels has not been examined. Using the isolated perfused fetoplacental cotyledon, we compared the vasoconstrictor responses to a thromboxane mimetic, U46619, in placentae from normal women and women with diabetes mellitus (classes C, D and R). Increases in perfusion pressure in response to bolus injections of U46619 were used to construct dose-response curves. The threshold dose of U46619 to cause a pressor response was similar in placentae from normal and diabetic pregnancies, but the slope of the dose-response curve was decreased by 39 per cent in placentae from diabetic pregnancies compared with normal controls (P < 0.01). To examine the potential contribution of altered thromboxane receptors, equilibrium binding studies were performed using the thromboxane antagonist [3H]-SQ29548 to a 44,000 g fraction of placental homogenate. The affinity of thromboxane receptors was significantly decreased in placentae from diabetic pregnancies compared with normal controls [Kd = 41.9 +/- 7.9, (n = 6) versus control, 21.4 +/- 1.3 nM (n = 26), P < 0.001]. In contrast, the density of thromboxane receptor sites was not significantly changed (diabetes, 176.0 +/- 6.2 versus control, 150.3 +/- 6.5 fmol/mg, P = not significant). Placental production of thromboxane and prostacyclin were measured by the incorporation of [14C]-arachidonic acid into [14C]-thromboxane B2 and [14C]-6-keto-prostaglandin F1 alpha, respectively. Incorporation of [14C]-arachidonic acid into both thromboxane B2 and 6-keto-prostaglandin F1 alpha was similar in placentae from diabetic and normal pregnancies. We conclude that vascular responsiveness to thromboxane is reduced in placentae from mothers with diabetes by a receptor-mediated mechanism. These changes may contribute to abnormalities in the regulation of fetoplacental haemodynamics, growth and development in pregnancies complicated by diabetes mellitus.
Placenta 1994 Dec
PMID:Reduced thromboxane receptor affinity and vasoconstrictor responses in placentae from diabetic pregnancies. 788 25

The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations.
Placenta 1994 Jan
PMID:Placental water content and distribution. 820 69

Our objective was to evaluate prostanoid release from the placentae of pregnancies complicated by severe intrauterine growth retardation (IUGR) and without hypertension, compared with placentae from normal, uncomplicated term pregnancies. A perifusion system was utilized to study the release of prostanoids 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2(TxB2), prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from human placentae from pregnancies complicated by normotensive severe IUGR (n = 9, five at term and four preterm) and normal control pregnancies (n = 6). For each placenta, triplicate chambers of tissue were perifused at a rate of 6 ml/h, and samples were collected from hours 5-10. Prostanoids were measured using specific and sensitive radioimmunoassays. In the IUGR group, the basal placental production of the vasoconstrictor thromboxane was not increased, nor was the ratio of cumulative TxB2 to 6-keto-PGF1 alpha elevated compared with normal term controls. In three term IUGR placentae, the ratio was significantly decreased compared with controls. The basal placental production of the vasoconstrictor PGF2 alpha was likewise not increased compared with controls, nor was the ratio of PGF2 alpha to PGE2 elevated. Two of the placentae in the term IUGR group demonstrated significant elevations of PGE2 and 6-keto-PGF1 alpha. Overall, the IUGR placentae released normal or low normal levels of the prostanoids studied. The pattern of placental prostanoid release over time was similar to that of the normal term placentae. The term and preterm placentae of pregnancies complicated by severe IUGR did not exhibit an excess production of vasoconstrictor prostanoids. Therefore, strategies designed to reduce thromboxane production in severe IUGR without hypertension may be unjustified.
Placenta 1995 Sep
PMID:Placental prostanoid release in severe intrauterine growth retardation. 857 May 72

Glucocorticoids play important roles in development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed category of 11 beta-hydroxysteroid dehydrogenase type2 (11 beta-HSD2, which potently inactivates glucocorticoids) and the mineralocorticoid receptor (MR) by in situ hybridisation from embryonic day 9.5 (E9.5, term = E19) until after birth in the mouse. Widespread abundant 11 beta-HSD2 mRNA expression from E9.5-E12.5 changes dramatically at approximately E13 to a limited tissue-specific pattern (kidney, hindgut, testis/bile ducts, lung and a few brain regions (later seen in cerebellum, thalamus, roof of midbrain, neuroepithelial regions in pons and near the subicular hippocampus)). Placenta (labyrinthine zone) and extra-embryonic membranes express abundant 11 beta-HSD2 mRNA until E15.5 but this ceases = E16.5. It is unclear to what extent rodent term placental 11 beta-HSD activity is due to persisting 11 beta-HSD2 protein. Convincing MR mRNA expression is seen from E13.5 and includes pituitary, heart, muscle and meninges with expression later in gut, kidney, thymus, discrete areas of lung and several brain regions (including hippocampus, rhinencephalon and hypothalamus). 11 beta-HSD2 and MR clearly co-localise = E18.5 in kidney and colon and might do so in discrete areas of lung (E14-15) and neuroepithelia near the subicular hippocampus. Probably elsewhere MR are non-selective and 11 beta-HSD2 is involved in protecting glucocorticoid receptors in fetal fetal tissues. Comparison with previous enzymology studies suggest the changing pattern of 11 beta-HSD2 mRNA is likely to be translated into enzyme activity and have significant parallels in human development.
 ...
PMID:The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. 859 33

The human placenta perfused in vitro with Krebs' solution has been used to examine the effects of low oxygen tension on the vasoreactivity of the fetal placental vessels to several vasodilator and vasocontrictor autacoids. Increases in fetal arterial perfusion pressure (FAP) produced by endothelin-1 (ET-1, human), the thromboxane A2-mimetic U46619, 5-hydroxytryptamine (5-HT), angiotensin II (A II) and bradykinin (BK) were examined under conditions of high ( >or= 450 mmHg) and low <or= 50 mmHg) O2 tension. Similarly, decreases in pressure produced by adenosine triphosphate (ATP) and arachidonic acid (AA) were examined. The effects of these autacoids on the fetoplacental vasculature during low oxygen perfusion was compared to that obtained following nitric oxide synthase inhibition with N omega-nitro-L-arginine, (L-NOARG, 100 microns). Increases in FAP caused by ET-1, U46619, and 5-HT on fetoplacental blood vessels were not altered significantly at low oxygen tension, although that in response to BK was enhanced. Increases in FAP caused by A II were unchanged at low oxygen tension. ATP-induced decreases in FAP were reduced whereas AA-mediated changes were unchanged. Both low oxygen tension and L-NOARG produced an elevation in basal perfusion pressure. Perfusion of the human placenta with Krebs' solution of low oxygen tension may compromise placental vascular function. Impaired placental oxygenation may contribute to the development and severity of vasoconstriction in the placenta associated with pre-eclampsia/pregnancy induced hypertension.
Placenta 1995 Dec
PMID:Effects of variation in oxygen tension on responses of the human fetoplacental vasculature to vasoactive agents in vitro. 871 Jul 98

The syncytiotrophoblast (ST) cell layer of the human villous placenta expresses nitric oxide (NO) synthase. Because NO is a potent relaxant of vascular smooth muscle and inhibitor of platelet activity, we postulated that exaggerated intervillous aggregation of platelets and reduced fetoplacental blood flow in pre-eclampsia result from reduced expression of NO synthase (and production of NO) by the ST. Conversion of [3H]arginine to [3H]citrulline and Lineweaver-Burk transformation were used to derive the Vmax and K(M) of NO synthase. Contrary to our expectations, the Vmax was not significantly different between villous placenta obtained from nulliparous normal and pre-eclamptic women (n = 11 each). The Vmax and K(M) were 22.3 +/- 2.3 pmol/mg per min and 1.3 +/- 0.1 microns, and 22.0 +/- 2.7 pmol/mg per min and 1.4 +/- 0.1 microns, for villous placenta from the nulliparous normal and pre-eclamptic women, respectively. The Vmax and K(M) of placental NO synthase were also comparable among multiparous normal and pre-eclamptic women, as well as women with gestational hypertension. When compared with the enzyme activity of the villous, that of the basal plate was reduced by approximately one-half in all placentae. The calcium-independent activity was consistently 40-fold less than the calcium-dependent activity, and it was similar between villous and basal plate, and between placentae from normal and hypertensive women. We suggest that expression of NO synthase is not different in placentae obtained from normal and pre-eclamptic women.
Placenta 1995 Dec
PMID:Nitric oxide synthase activity in placentae from women with pre-eclampsia. 871 Aug


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