iloprost and Pre-Eclampsia

This study was designed to determine the effects of cyclooxygenase inhibition and prostacyclin agonists on the hypertension induced by nitric oxide synthase blockade in a previously characterized rat model of preeclampsia.. A condition similar to preeclampsia was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N G -nitro- L -arginine methyl ester through subcutaneously implanted osmotic minipumps. Blood pressure was measured with the tail cuff method. In the first experiment the rats received either vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), indomethacin (0.1 mg/d), or N G -nitro- L -arginine methyl ester plus indomethacin beginning on day 17 of pregnancy. In the second experiment the rats received vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), or N G -nitro- L -arginine methyl ester plus iloprost (31 microgram/d). In a third experiment cicaprost (15 microgram/d) was substituted for iloprost.. Except for an increase on the day after insertion of the pump indomethacin had no significant effect on the hypertension induced by N G -nitro- L -arginine methyl ester. Both prostacyclin agonists (iloprost and cicaprost), however, attenuated the rise in blood pressure usually seen after N G -nitro- L -arginine methyl ester administration.. Nonselective inhibition of the cyclooxygenase enzymatic system does not influence the hypertension seen in the rat preeclampsia model induced by chronic nitric oxide deficiency. The hypertension in this model can be partially reversed with prostacyclin analogs.

Topics: Animals; Blood Pressure; Cyclooxygenase Inhibitors; Disease Models, Animal; Enzyme Inhibitors; Epoprostenol; Female; Gestational Age; Iloprost; Indomethacin; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pre-Eclampsia; Pregnancy; Prostaglandins, Synthetic; Rats

Prostacyclin (PGI2) 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 PGI2 receptor number. In contrast, the binding affinity to the PGI2 mimetic iloprost was considerably reduced in pre-eclampsia, whereas receptor affinity between PIH and normal pregnancy did not differ significantly.

Topics: Adult; Birth Weight; Blood Platelets; Epoprostenol; Female; Humans; Hypertension; Iloprost; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Protein Binding; Receptors, Epoprostenol; Receptors, Prostaglandin

1. Platelet behaviour in vitro in relation to cyclic AMP was studied longitudinally during pregnancy and in the same women when they were not pregnant. Subjects comprised a group of healthy primigravidae and a group of women deemed at risk of pre-eclampsia, on the basis of a previous history of the condition. 2. There was a progressive decline during pregnancy in sensitivity of platelets to inhibition of the arachidonic acid-induced release reaction by agents which act via cyclic AMP. This effect was maximum at 36 weeks' gestation. 3. Basal platelet cyclic AMP levels, and those in the presence of a phosphodiesterase inhibitor, did not change throughout the period of the study. 4. By contrast, platelet cyclic AMP accumulation in response to a variety of adenylate cyclase stimulators was reduced from early pregnancy, throughout the gestational period, compared with post-natally. This effect was noted when platelets were incubated with prostaglandins acting via different surface receptors or with forskolin and was most marked on co-incubation with a phosphodiesterase inhibitor. 5. Compared with healthy women, platelets from women with a previous history of pre-eclampsia tended to accumulate less cyclic AMP in response to adenylate cyclase stimulators. This was the case both during pregnancy and post-natally. Further investigation of adenylate cyclase activity in platelets in relation to pre-eclampsia is required.

Topics: Adenylyl Cyclases; Adult; Arachidonic Acid; Blood Platelets; Cyclic AMP; Female; Humans; Iloprost; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Pregnancy, High-Risk; Prospective Studies; Prostaglandin D2; Risk Factors; Serotonin; Thromboxane B2

The hypothesis that preeclampsia may be associated with an increase in the response of the placental arteries to vasoconstrictors or a decrease in their response to vasodilators was tested.. Concentration-response curves to various agents were determined on helical strips of fetal placental arteries from normotensive (n = 33) and preeclamptic (n = 8) women to calculate the potencies and maximal effects of the agents.. Endothelin, prostaglandin F2 alpha, and serotonin caused concentration-dependent contractions; angiotensin II and norepinephrine produced little or no effects. The prostacyclin analog iloprost and atrial natriuretic factor, but not isoproterenol, relaxed placental arteries. Iloprost was more effective on preeclamptic than on normal arteries, but the effects of other agents on the two groups of arteries did not differ. Placental arteries exhibited spontaneous oscillations that were more marked in preeclamptic than in normal arteries and were inhibited by indomethacin.. Preeclampsia is not associated with an increase in the responses of fetal placental arteries to vasoconstrictors or a decrease in their response to vasodilators. However, placental arteries from preeclamptic subjects exhibit increased oscillations.

Topics: Adult; Angiotensin II; Arteries; Atrial Natriuretic Factor; Dinoprost; Endothelins; Female; Humans; Iloprost; Isoproterenol; Norepinephrine; Placenta; Pre-Eclampsia; Pregnancy; Serotonin; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

1. Platelet activation in vivo occurs in healthy pregnant women and is more marked in women with preeclampsia. During pregnancy platelets have also been shown in vitro to be less susceptible to the inhibitory effects of prostacyclin. The cyclic nucleotide cyclic AMP has a key role as an inhibitory second messenger in platelets and mediates the inhibitory effects of prostacyclin. 2. We have studied cyclic AMP in relation to platelet behaviour in healthy pregnant women in the third trimester and in women with pregnancy-induced hypertension and pre-eclampsia. Non-pregnant young women were used as controls. 3. Pharmacological agents which increase levels of cyclic AMP were significantly less effective as inhibitors of platelet activation during pregnancy, but there was no difference between the healthy and hypertensive pregnant subjects. 4. Basal platelet cyclic AMP levels were the same in all three groups. However, the production of cyclic AMP in response to a range of adenylate cyclase stimulators was reduced during pregnancy, but again there was no difference between healthy and hypertensive pregnant subjects. 5. The reduction in platelet cyclic AMP levels in pregnancy occurred not only with those adenylate cyclase stimulators which operate via surface receptors, but also on direct stimulation of the enzyme with forskolin. 6. The most likely explanation of these observations is a reduction in the ability of the platelet adenylate cyclase enzyme to respond to stimulation of the third trimester of pregnancy. The consequent reduction in formation of the inhibitory second messenger cyclic AMP may in part be responsible for platelet activation in vivo during pregnancy. There does not appear to be a further difference in platelet cyclic AMP production in hypertensive pregnant women.

Topics: Adenylyl Cyclases; Adult; Arachidonic Acids; Blood Platelets; Cross-Sectional Studies; Cyclic AMP; Female; Humans; Iloprost; Platelet Activation; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Thromboxane B2

Platelet sensitivity to a prostacyclin analogue (PSP) was investigated at different stages of normal and pathological pregnancies. During uncomplicated pregnancy PSP decreased progressively by about 30% and returned to almost normal values in the puerperium. In pre-eclamptic women PSP was reduced by 49% and in pregnant diabetics by 50% compared with normal pregnant individuals of corresponding gestational age. Reduced PSP in normal and pathological pregnancy seems to be another aspect of increased coagulability and platelet aggregation found in these patients.

Topics: Blood Platelets; Depression, Chemical; Epoprostenol; Female; Gestational Age; Humans; Iloprost; Platelet Aggregation; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics