Platelet PGI₂ receptor affinity is reduced in pre‐eclampsia

Abstract

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...

Circulating Factors as Markers and Mediators of Endothelial Cell Dysfunction in Preeclampsia

“…However, the binding affinity of these receptors for the PGI 2 -mimetic iloprost was considerably reduced in preeclampsia compared with the other two groups. 129 Retrospective cohort studies of women with renal disease in pregnancy indicated that the incidence of preeclampsia was significantly less common in women treated prophylactically with heparin or aspirin. 130 Initial trials of low-dose aspirin in high-risk subjects appeared promising in the prevention of preeclampsia.…”

Pharmacogenetics and Pharmacogenomics Impact on Aspirin Response

“…Insufficient production of prostacyclin (PGI2) during early gestation is linked to the pathophysiology of pregnancyinduced hypertension (PIH). Aspirin, due to its anti-inflammatory and anticoagulant properties, is suggested as a possible effective treatment option for Preeclampsia [76][77][78][79][80][81][82][83]. Aspirin's ability to cross the placenta and work at 50-150 mg makes it a useful therapy, but >75 mg/day is better [84].…”

Prostacyclin Deficiency and Reduced Fetoplacental Blood Flow in Pregnancy-Induced Hypertension and Preeclampsia

“…Prostacyclin (PGI 2 ) may play a role in altered platelet-vessel wall interaction since reduced endothelial generation of this vasodilator and inhibitor of platelet function is well established in the disease [4,5]. Furthermore, there is no basis for the assumption that compensatory alterations at the receptor level counterbalance PGI 2 Klockenbusch/Goecke/Krüssel/Tutschek/ Crombach/Schrör deficiency in pregnancy-induced hypertension (PIH) and preeclampsia [6]. It is, however, uncertain whether PGI 2 really acts as an important mediator of blood flow in pregnancy.…”