Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

Pedersen, E. B.; Christensen, N. J.; Christensen, Poul; Johannesen, P.; Kornerup, H. J.; Kristensen, Søren Risom; Lauritsen, Jakob; Leyssac, P. P.; Rasmussen, A. B.; Wohlert, M

doi:10.1161/01.hyp.5.1.105

Cited by 90 publications

(28 citation statements)

References 36 publications

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“…Urinary excretion of TXB 2 , on the other hand, showed no significant difference in PIH and in normal pregnancy. Our results are consistent with those reported by Pedersen et al, 8 at least as far as PGEj is concerned.…”

Section: Discussionsupporting

confidence: 94%

“…The method has been partly described previously 13 : 20-ml urine samples were centrifuged (for 10 minutes at 1000 g) and acidified with citric acid (pH 3.0-3.4); approximately 6000 dpm of [ 3 H]6-keto-PGF la (150 Ci/mmol, Buckinghamshire, Amersham, UK) was then added to each sample. As a first chromatographic step, the urine samples were passed through Sep-Pak C, 8 cartridges (Waters, Milford, MA, USA), pretreated with ethanol (20 ml) and water (20 ml). All solvents used were analytical grade (ACS Carlo Erba, Milan, Italy).…”

Section: Laboratory Proceduresmentioning

confidence: 99%

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Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

et al. 1988

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SUMMARY The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A 2 were measured, along with renal prostaglandin E 2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E 2 , 6-keto-prostaglandin F lcr , and 2,3-dinor-6-ketoprostaglandin F, a were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B 2 and 2,3-dinor-thromboxane B 2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p< 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F, a and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II. is defined as systemic arterial hypertension (diastolic blood pressure > 85 mm Hg or mean blood pressure > 9 5 mm Hg) appearing in the third trimester of pregnancy, often associated with edema and proteinuria.' A number of hypotheses have been advanced regarding the pathogenesis of PIH, but the ultimate mechanism responsible for blood pressure elevation is still unknown. PIH has been attributed to one or more of the following factors: impaired renal function, 2 inappropriate activation of the renin-angiotensin-aldosterone system, 3 and decreased production of progestational compounds. 4 By acting as vasodilators and natriuretic factors, prostaglandin E 2 (PGE 2 ) and kinins might in some way be involved in the regulation of plasma volume. 9 -l0 Vasodilator prostaglandins, particularly prostacyclin (PGI 2 ), appear to play an important role in the control of vascular reactivity, platelet aggregability, and renal and uteroplacental blood flow during normal pregnancy, whereas thromboxane A 2 (TXA 2 ) is known to have the opposite effect." An imbalance between these two compounds might account for some of the phenomena characterizing PIH. On the basis of these observations, then, the renal prostaglandin system appears to be somehow involved in the sequence of events leading to the full clinical development of PIH. Since renal involvement in PIH is not enough in itself to account for systemic hypertension, the aim of our study was to evaluate not only the urinary excretion of PGE 2 , kallikrein, and the renal metabolites of PGI 2 and TXA 2 , but also the 2,3-dinor metabolites of PGI 2 and TXA 2 deriving from the systemic production

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Section: Discussionsupporting

confidence: 94%

Section: Laboratory Proceduresmentioning

confidence: 99%

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

et al. 1988

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“…Liddle syndrome of hypertension with suppressed aldosterone in which ENaC remains membrane-associated illustrates the significance of dysregulated ENaC for blood pressure. 20 A pathophysiological mechanism that includes ENaC-mediated, excessive renal conservation of NaCl in preeclampsia is consistent with a number of previous observations: (1) plasma renin and aldosterone is suppressed with temporal correlation between onset of proteinuria and suppression of renin and aldosterone; 21,22 (2) extracellular volume expansion with elevated atrial natriuretic peptide; [22][23][24] (3) more avid retention of NaCl after NaCl infusion; 15,25 and (4) release to postural changes. 16,26 The K + -sparing antihypertensive drug amiloride normalizes sodium balance and resolves edema in a rat model of nephrotic syndrome 1,4 and in children with nephrotic syndrome.…”

Section: Discussionsupporting

confidence: 87%

Urinary Plasmin Activates Collecting Duct ENaC Current in Preeclampsia

et al. 2012

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In nephrotic syndrome, plasminogen is aberrantly filtered from plasma to the urinary space and activated along the tubular system. In vitro, plasmin increases ENaC current by proteolytic cleavage of the γ-subunit. It was hypothesized that preeclampsia is associated with plasmin-dependent ability of tubular fluid to activate ENaC. Urine was sampled from 16 preeclamptic (PE) patients and 17 normotensive pregnant women (Ctrl). Urine was analyzed for plasmin(ogen), creatinine, albumin, aldosterone, Na + , K + , proteolytic activity, and for its effect on inward current in cortical collecting duct cells (M1 cells) by whole-cell patch clamp. In PE, urine plasmin(ogen): creatinine ratio was elevated 40-fold (geometric mean, 160 versus 4 µg/g; P <0.0001) and urine aldosterone: creatinine ratio was suppressed to 25% of Ctrl (geometric mean, 27 versus 109 µg/g; P <0.001). A significant negative correlation was found in PE between urinary plasmin(ogen) and aldosterone ( P <0.05). In PE, proteolytic activity was detected at 90 to 75 kD by gelatin zymography in 14 of 16 patients and confirmed by serine protease assay. Immunoblotting showed active plasmin in PE urine. Whole-cell inward current increased in M1 cells on exposure to urine from PE (173±21%; n=6; P <0.001). The increase in current was abolished by amiloride (2 μmol/L; P <0.001), α 2 -antiplasmin (1 μmol/L; P <0.001), and heat denaturation ( P <0.001). Preeclampsia is associated with urinary excretion of plasmin(ogen) and plasmin-dependent activation of ENaC by urine. Proteolytic activation of ENaC by plasmin may contribute to Na + retention and hypertension in preeclampsia.

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“…Activation of 15-LOX results in the production of 15-(S)-HETE (hydroxyeicosatetraenoic acid), which increases COX2 expression and PGE2 production. During preeclampsia, the urinary excretion of PGE2 is reduced, [34][35][36] but the correlation between circulating levels of PlGF and PGE2 has never been studied.…”

Section: Discussionmentioning

confidence: 99%

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

et al. 2016

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Abstract-The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture. Laminar and continuous FSS (1 dyn cm −2) was applied to human syncytiotrophoblasts cultured in a parallel-plate flow chambers. Secreted levels of PlGF, sFlt-1 (soluble fmslike tyrosin kinase-1), and prostaglandin E2 were tested by immunologic assay. PlGF levels of mRNA and intracellular protein were examined by RT-PCR and Western blot, respectively. Intracellular cAMP levels were examined by timeresolved fluorescence resonance energy transfer cAMP accumulation assay. Production of cAMP and PlGF secretion was significantly increased in FSS conditions compared with static conditions. Western blot analysis of cell extracts exposed to FSS showed an increased phosphorylation of protein kinase A substrates and cAMP response element-binding protein on serine 133. FSS-induced phosphorylation of cAMP response element-binding protein and upregulation of PlGF were prevented by inhibition of protein kinase A with H89 (3 μmol/L). FSS also triggers intracellular calcium flux, which increases the synthesis and release of prostaglandin E2. The enhanced intracellular cAMP in FSS conditions was blocked by COX1/COX2 (cyclooxygenase) inhibitors, suggesting that the increase in prostaglandin E2 production could activate the cAMP/protein kinase A pathway in an autocrine/paracrine fashion. FSS activates the cAMP/protein kinase A pathway leading to upregulation of PlGF in human syncytiotrophoblast.

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Preeclampsia -- a state of prostaglandin deficiency? Urinary prostaglandin excretion, the renin-aldosterone system, and circulating catecholamines in preeclampsia.

Cited by 90 publications

References 36 publications

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

Urinary Plasmin Activates Collecting Duct ENaC Current in Preeclampsia

Fluid Shear Stress Promotes Placental Growth Factor Upregulation in Human Syncytiotrophoblast Through the cAMP–PKA Signaling Pathway

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