Reduced umbilical artery prostacyclin formation in complicated pregnancies

Dadak, Christian; Kefalides, A; Sinzinger, H.; Weber, G.

doi:10.1016/0002-9378(82)90354-4

Cited by 80 publications

(14 citation statements)

References 18 publications

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“…Unfortunately, the patients with pre-eclampsia have not been evaluated by subgroup analysis. More clear evidence in favour of PGI 2 receptor in this disorder [8,9 ], which agrees with the reduced …”

Section: Resultssupporting

confidence: 74%

Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Klockenbusch

Hohlfeld²,

Wilhelm³

et al. 1996

Brit J Clinical Pharma

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Platelet PGI 2 receptor affinity is reduced in pre-eclampsia WALTER KLOCKENBUSCH2, THOMAS HOHLFELD1, MICHAEL WILHELM1, THIERRY SOMVILLE2 & KARSTEN SCHRÖ R1 1Institut für Pharmakologie and 2Frauenklinik, Heinrich-Heine-Universitä t Dü sseldorf, Dü sseldorf, GermanyProstacyclin (PGI 2 ) receptors were studied in platelet membrane preparations from women with normal pregnancy, pregnancy-induced hypertension (PIH) or pre-eclampsia. Patient groups showed no differences in gestational week at delivery. A markedly lower birth weight, however, was found in pre-eclampsia. No differences between groups could be detected in platelet PGI 2 receptor number. In contrast, the binding affinity to the PGI 2 mimetic iloprost was considerably reduced in pre-eclampsia, whereas receptor affinity between PIH and normal pregnancy did not differ significantly.Keywords prostacyclin receptor platelets pregnancy-induced hypertension preeclampsiaIntroduction from an antecubital vein into a syringe containing 10 ml acid citrate/dextrose (ACD, BiostabilA, Biotest, Frankfurt, Germany). Platelet-rich plasma was prepared Reduced formation of PGI 2 is a typical feature of PIH and pre-eclampsia [1,2 ]. It is, however, still unsettled by centrifugation (250 g, 10 min, 20°C). The pH was adjusted to 6.5 with ACD. After a final centrifugation whether possible consequences of PGI 2 deficiency such as platelet activation, reduced blood flow and intrauter-(900 g, 10 min, 20°C) the supernatant was removed and the pellet stored at −80°C. Platelet membranes were ine growth retardation may be counterbalanced by increased number and avidity of corresponding recepprepared by repeated freezing and thawing and isolated by differential centrifugation [3 ]. tors. So far nobody has investigated PGI 2 receptors in pregnancies complicated by hypertension. The present For ligand binding studies [ 4], the pellets were resuspended in washing buffer (mm): NaCl (140), KCl study was designed to determine platelet PGI 2 receptor characteristics in normal pregnancy, PIH and pre-(5 ), Tris (10 ), sodium citrate (2 ), glucose (5 ), citric acid (5 ), pH 7.4 and centrifuged (105000 g, 15 min, 4°C). eclampsia and to assess any relation to the clinical outcome.Thereafter, the pellets were resuspended in assay buffer (mm): NaCl (140), KCl (5), Tris (10), glucose (5 ), CaCl 2 (5 ), pH 6.0. Membrane suspensions (100 ml ) were incubated with 50 ml [3H]-iloprost (5 nm, Amersham, Braunschweig, Germany) and 50 ml of unlabelled iloprost Methods (Schering, Berlin, Germany) at concentrations of 1-10 000 nm (final) for 90 min at 15°C. Bound ligand was Patients were randomly selected from the local department of obstetrics and comprised 15 healthy pregnant separated from free by rapid filtration (Brandel cell harvester, Gaithersburg, USA). Radioactivity was measwomen, nine patients with PIH and 10 with preeclampsia. Informed consent was obtained from all ured by liquid scintillation counting. Binding affinity (K d −1) and capacity (B max ) were calculated from the individuals. Hypertension w...

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Section: Resultssupporting

confidence: 74%

Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Klockenbusch

Hohlfeld²,

Wilhelm³

et al. 1996

Brit J Clinical Pharma

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“…The finding of increased platelet aggregation and release of malonyldialdehyde in newborn infants and their diabetic mothers compared with control mother-neonate pairs provides further evidence of enhanced thromboxane synthesis activity (42). In contrast to increased synthesis of these proaggregatory eicosanoids by platelets, release of the potent antiaggregatory eicosanoid prostacyclin was decreased in arteries (25) and veins (26) of patients with diabetes mellitus, in umbilical arteries of neonates of mothers with either gestational or juvenile-onset diabetes (43,44), and in aortic tissues obtained from rats (45,46) and swine (47) with streptozotocin-induced diabetes. In the pancreas a possible role for abnormalities of PG metabolism in the pathophysiology of impaired insulin secretion in diabetics has been inferred from the observation that PGE infusion inhibits glucose-induced acute insulin responses in normal human subjects and infusion of sodium salicylate partially restores the acute insulin response to glucose infusion in type II diabetics (48).…”

Section: Discussionmentioning

confidence: 99%

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Schambelan¹,

Blake²,

Sraer³

et al. 1985

J. Clin. Invest.

176

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Abnormalities in glomerular function have been observed frequently in the early stages of both clinical and experimental diabetes mellitus. Because prostaglandins (PGs) are present in the glomerulus and have profound effects on glomerular hemodynamics, and because abnormalities of PG metabolism have been noted in other tissues from diabetics, we studied PG biosynthesis in glomeruli obtained from rats in the early stages of experimental diabetes mellitus. Streptozotocin, 60 mg/kg, was administered intravenously to male Sprague-Dawley rats. Control rats received an equal volume of the vehicle. Glomeruli were isolated 9-23 d later. Production of eicosanoids was determined by two methods: by direct radioimmunoassay after incubation of glomeruli under basal conditions and in the presence of arachidonic acid (C20:4), 30 pM, and by radiometric high-performance liquid chromatography (HPLC) after incubation of glomeruli with ['4C]C20:4. When assessed by radioimmunoassay, mean basal production of both prostaglandin E2 (PGE2) and prostaglandin F2. (PGF2.) was twofold greater in the diabetic animals whereas production of thromboxane B2 (TXB2) was not significantly greater than control. In response to C20:4, both PGE2 and PGF7, were also greater in the diabetic animals, but these differences were not statistically significant. The increased rate of basal PG production did not appear to be related directly to the severity of the diabetic state as reflected by the degree of hyperglycemia at the time of sacrifice. In fact, the rates of glomerular PG production in the individual diabetic animals correlated inversely with the plasma glucose concentration. The increased rate of PG synthesis did not appear to be due to a nonspecific effect of streptozotocin inasmuch as glomerular PG production was not increased significantly in streptozotocin-treated rats which were made euglycemic by insulin therapy. Furthermore, addition of streptozotocin, 1-10 mM, to the incubation media had no effect on PGE2 production by normal glomeruli. PGE2 production by normal glomeruli was also not influenced by varying the glucose concentration in the incubation media over a range of 1-40 mM. When metabolism of I'4C1C20:4 was evaluated by high-performance liquid chromatography conversion to labeled PGE2, PGFu,, TXB2, and hydroxyheptadecatrienoic acid by diabetic glomeruli was two-to threefold greater compared with that in control glomeruli, whereas no significant difference in conversion to 12-and 15-hydroxyeicosatetraenoic acid occurred. These findings indicate that glomerular cyclooxygenase but not lipoxygenase activity was increased in the diabetic animals. A concomitant increase in glomerular phospholipase activity may also have been present to account for the more pronounced differences in PG production noted in the absence of exogenous unlabeled C20:4. These abnormalities in PG biosynthesis by diabetic glomeruli may contribute to the altered glomerular hemodynamics in this pathophysiologic setting.

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“…It is well established in pre eclampsia that there is a relative increase in vasoconstricting, platelet-aggregating prostaglandins (thromboxane A2 and PGF2) and similar alterations arc seen in diabetes mellitus [16]. Vascular prostacyclin (PGU) synthesis is decreased and platelet synthesis of thromboxane A2 is increased in both patients and experimental animals with diabetes mellitus [17].…”

Section: Discussionmentioning

confidence: 99%

Hypertensive Disorders in Pregnant Women with Diabetes mellitus

Rudge¹,

Calderon²,

Ramos³

et al. 1997

Gynecol Obstet Invest

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The present study was performed to assess the rate of hypertensive complications in diabetic pregnant patients and the influence of White’s classification and the quality of the diabetic control. This study included 169 diabetic pregnant women who had delivered at the University Hospital of Botucatu Brazil from 1980 to 1981. The hypertensive disorders occurred in 29.8% of the cases. The incidence of the hypertensive process was the same in all classes of diabetic patients, and it was independent of the glycemic control. In patients with gestational diabetes (classes A and AB), chronic hypertension was the commnest type found; in patients with short-term diabetes (classes B and C) pregnancy-induced hypertension (PIH) and chronic hypertension with superimposed PIH was the most frequent type, and diabetic patients with vasculopathies (classes D-R) had preeclampsia and chronic hypertension with superimposed preeclampsia as the commonest type found.

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Reduced umbilical artery prostacyclin formation in complicated pregnancies

Cited by 80 publications

References 18 publications

Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Hypertensive Disorders in Pregnant Women with Diabetes mellitus

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Reduced umbilical artery prostacyclin formation in complicated pregnancies

Cited by 80 publications

References 18 publications

Platelet PGI2 receptor affinity is reduced in pre‐eclampsia

Platelet PGI2 receptor affinity is reduced in pre‐eclampsia

Increased prostaglandin production by glomeruli isolated from rats with streptozotocin-induced diabetes mellitus.

Hypertensive Disorders in Pregnant Women with Diabetes mellitus

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Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia