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A prospective study investigated platelet cytosolic calcium in non-pregnant volunteers (n = 30) and samples from the umbilical veins of babies from both normotensive (n = 18) and hypertensive (n = 15) primigravidae, and their mothers. There was no significant difference between the neonatal umbilical venous platelet cytosolic calcium concentration (p[Ca2+]i) in babies born to normotensive primigravidae or to those whose pregnancies were complicated by gestational hypertension (88 x 9 (SE) 2 x 5) in normotensive primagravidae, 80 x 6 (2 x 8) in pregnancy induced hypertension without proteinuria, and 89 x 3 (3 x 2) nmol/l in pre-eclampsia. There was also no significant difference in the p[Ca2+]i from the umbilical veins of the pregnancies studied and those of non-pregnant female volunteers in the follicular phase of their menstrual cycle. This was despite a gradual and significant rise in p[Ca2+]i with increasing severity of disease in the mothers of the babies studied (119 x 9 (4 x 1) in normotensive primagravidae, 130 x 8 (7 x 3) in pregnancy induced hypertension without proteinuria, and 148 x 2 (4 x 5 ) nmol/l in pre-eclampsia). The mean maternal p[Ca2+]i in the three samples returned to concentrations comparable with those in non-pregnant subjects by 12 weeks after birth. These data demonstrate no significant difference between the mean p[Ca2+]i in non-pregnant women and those obtained from the umbilical venous blood of normotensive or hypertensive primigravidae. They suggest that the functional hypoactivity of neonatal platelets is probably not secondary to a decrease in basal p[Ca2+]i. They also suggest that the progressively raised p[Ca2+]i in normal and hypertensive pregnancies might be due to a pregnancy specific factor that does not cross the placenta,

Five pregnant women whose pregnancies were complicated only by essential hypertension had significantly elevated platelet cytosolic calcium levels as compared with those of their normotensive counterparts. There seems to be an association between platelet cytosolic calcium level and arterial blood pressure that has previously been described in both nonpregnant and preeclamptic women.

Objective: To determine if platelet intracellular free calcium concentration (p.(Ca2+)i) changes with gestation in normotensive, uncomplicated pregnancy., Design: A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulliparous nonpregnant volunteers., Setting: The antenatal clinic at University Hospital, Queen's Medical Centre, Nottingham., Subjects: Two groups of women were studied. Thirty-one nulliparous, nonpregnant women not using oral contraception were investigated in the early follicular phase of their menstrual cycles. Also, 24 primigravid women with normotensive, uncomplicated pregnancies were investigated on eight separate occasions during their pregnancies., Results: A significant increase in mean p.(Ca2+)i was demonstrated by 28 weeks gestation in the pregnant women as compared to the nonpregnant control group and the same individuals when investigated at 12 weeks postpartum (P < 0.05; ANOVA). This change was maximal at 36 weeks gestation (P < 0.001; ANOVA); concentrations had returned to those not significantly different from nonpregnant women by six weeks postpartum., Conclusions: Basal platelet (Ca2+)i increases significantly by the third trimester of normal, primigravid pregnancy as compared to pregnancy values and postnatal values. These data mirror the previously described observations of platelet behaviour noting increased activity at this gestation of pregnancy. It may be that the increased basal p.(Ca2+)i indicates that smaller transient signals have to be generated to induce platelet activity, such as shape change, aggregation and exocytosis.

Objectives: The primary objective of this study was to determine the baseline platelet intracellular free Ca2+ concentration in normotensive and hypertensive primigravid women and to note any correlation between variables (ie. platelet intracellular free Ca2+ concentration and arterial blood pressure)., Design: A cross-sectional study of 24 normotensive and 36 primiparous women whose pregnancies were complicated by gestational hypertension, in the third trimester., Methods: Platelet intracellular free Ca2+, serum Ca2+, and renal clearance of Ca2+ were recorded., Results: Mean platelet intracellular free Ca2+ concentration was significantly increased in those subjects whose pregnancies were complicated by proteinuric gestational hypertension (pre-eclampsia) compared with the normotensive primiparous control sample. Those subjects with non-proteinuric pregnancy-induced hypertension did not show this significant increase in baseline platelet intracellular free Ca2+ concentration despite having a persistent and statistically significantly elevated systemic arterial blood pressure. On pooling these data for both normotensive and hypertensive primigravidae a significant positive correlation was noted between the variables of platelet intracellular free Ca2+ concentration and arterial blood pressure. The renal clearance of free Ca2+ was progressively reduced with increasing severity of the disease but had returned to normal 6 weeks postpartum. Serum Ca2+ concentrations corrected for albumin were however higher in the hypertensive patients., Conclusion: Transmembrane Ca2+ fluxes are altered in hypertensive pregnancy by a specific mechanism, probably of placental origin.

Serial estimations of platelet angiotensin II binding were made in two patients with hypertension developing in the third trimester of pregnancy. The fall in platelet angiotensin II binding that is seen in normotensive pregnancy did not occur in these two patients.

1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined. 2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P less than 0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness. 3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P less than 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments. 4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.

1. Platelet angiotensin II binding, circulating angiotensin II levels, plasma renin substrate and plasma renin concentration were measured in a longitudinal study of 30 women during pregnancy and the puerperium. 2. There was a significant fall in platelet angiotensin II binding from 11 weeks gestation to 18 weeks gestation (P less than 0.01). There were no further significant changes in platelet angiotensin II binding until after delivery, a significant rise in platelet angiotensin II binding being found at 6 weeks post partum as compared with at 36 weeks gestation (P less than 0.01). There was no further significant change from 6 to 12 weeks post partum, and platelet angiotensin II binding at 6 and 12 weeks post partum in the pregnant cohort approximated to that in nonpregnant women. These changes parallel those known to occur in pressor responsiveness to angiotensin II in pregnancy. 3. Plasma angiotensin II concentration, plasma renin substrate and plasma renin concentration were all significantly higher during pregnancy than in the puerperium (P less than 0.001). There were no significant changes during pregnancy in plasma angiotensin II concentration or plasma renin concentration, although plasma renin substrate rose throughout. 4. Significant inverse correlations between platelet angiotensin II binding and plasma angiotensin II concentration (P less than 0.01), plasma renin substrate (P less than 0.01) and plasma renin concentration (P less than 0 greater than 001) were found during pregnancy. These data suggest that down-regulation of platelet angiotensin II binding by the components of the renin-angiotensin system pertains in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: The primary objective of this study was to determine the effect of i.v. angiotensin II infusion on platelet intracellular free calcium concentration in potentially hypertensive primigravid women., Design: Patients at 28-32 weeks gestation were selected on the basis of a diastolic pressure less than or equal to 80 mmHg taken at the antenatal clinic visit., Methods: An angiotensin II infusion test (4-16 ng/kg per min) was performed in 13 women. Platelet intracellular free calcium concentration, platelet angiotensin II binding site density and plasma angiotensin II concentration were measured before and at the end of the infusion. Pregnancy outcome (normotension or hypertension) was recorded., Results: Platelet intracellular free calcium concentration rose in 12 of 13 women during angiotensin II infusion. This rise was not directly correlated with initial or final platelet angiotensin II binding site density, plasma angiotensin II concentration or the evoked change in systolic or diastolic blood pressure. Five women subsequently developed pregnancy-induced hypertension. Although basal platelet intracellular free calcium concentration did not differ between the two groups, platelet intracellular free calcium concentration rose twice as much in response to angiotensin II in the five hypertensive pregnant women. There was a 12-fold increase in platelet angiotensin II binding in the future hypertensives, although basal angiotensin II was the same in the two groups., Conclusion: The enhanced rise in platelet intracellular free calcium concentration in response to angiotensin II administration in women who subsequently became hypertensive, together with their increased angiotensin II binding site density suggest a possible enhanced stimulus-effect coupling. Pregnancy-induced hypertension is a state of marked vasoconstriction, with an enhanced pressor response to angiotensin II. These data supply grounds for a hypothesis concerning the mechanism.

Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy.

A longitudinal study of platelet behaviour (platelet aggregation and release reaction) in whole blood and of serum thromboxane B2 production was performed before, during and after normal pregnancy. The response of platelets to arachidonic acid and to adrenaline was significantly increased in the third trimester. Six weeks after delivery, values were still modestly increased but return to non-pregnant values was complete by 12 weeks. Serum thromboxane B2 production was unchanged throughout pregnancy and the puerperium.

1. The results are presented of a cross-sectional study of 25 non-pregnant and 125 pregnant/postnatal women in whom platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration and plasma renin substrate were measured. 2. Platelet angiotensin II binding was significantly lower in the first-trimester patients as compared with the non-pregnant women (P less than 0.001). Specific binding remained low in the second and third trimesters, and in those patients studied 24 h after delivery. However, higher values, approximating to the non-pregnant level, were found 6 weeks postnatally (n = 25 for each group). 3. Plasma angiotensin II, plasma renin concentration and plasma renin substrate increased in pregnancy, with the increase becoming statistically significant as compared with the non-pregnant women in the second trimester. Maximal median values of plasma angiotensin II and plasma renin substrate were found in the third trimester, but maximal median values of plasma renin concentration were found in the second trimester. The concentrations of all three hormones fell after delivery. 4. There was an inverse correlation between platelet angiotensin II binding and simultaneously measured endogenous levels of plasma angiotensin II (P less than 0.02) and plasma renin substrate (P less than 0.05) in the 25 non-pregnant subjects. These findings support the concept of the angiotensin II receptor concentration being regulated by the plasma angiotensin II level. There was no correlation between platelet angiotensin II binding and plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The intracellular free calcium concentration ([Ca2+]i) in washed human platelets was measured using the fluorescent indicator, fura-2, in a cross-sectional study of 36 normotensive, primigravid volunteers, 12 in each trimester of pregnancy and a further 12 at 6 weeks post partum. The results were compared with those obtained from 30 normal female volunteers not using oral contraception. 2. The mean basal [Ca2+]i in the platelets of the pregnant women in the first two trimesters (115.6 +/- 6.7 and 120.1 +/- 5.7 nmol/l, respectively) was not shown to differ significantly from that of normal non-pregnant volunteers (112.3 +/- 2.9 nmol/l). However, during the third trimester a significant increase in [Ca2+]i was noted (134.0 +/- 4.9 nmol/l; P less than 0.05), with a return to normal values in the post-partum period (108.2 +/- 6.1 nmol/l). 3. [Ca2+]i was also measured in the platelets of a group of 12 primigravid pregnant women in the third trimester whose pregnancies were complicated by gestational hypertension (pregnancy-induced hypertension and pre-eclampsia). A significant rise in basal [Ca2+]i was noted in the platelets of primigravidae whose pregnancies were complicated by pre-eclampsia (163.6 +/- 8.8 nmol/l) as compared with normotensive, third-trimester primigravidae (P less than 0.02). However, no correlation could be demonstrated between [Ca2+]i and systemic blood pressure.

Blood platelet behaviour was compared in mothers at birth and their babies, and in non-pregnant, female controls. Platelet responses to arachidonic acid (AA) and to adrenaline were measured in platelet-rich plasma and the inhibitory effects of prostacyclin (PGI2) were determined. Platelets from the mothers differed from those from the neonates and controls in that lower concentrations of AA were needed to induce platelet aggregation and a release reaction. In addition, more PGI2 was needed to inhibit AA-induced platelet aggregation. Platelets from the neonates differed from the mothers and controls in that they were almost completely insensitive to adrenaline. They did not differ from the controls in their sensitivity to AA or PGI2 but the extent of the release reaction induced by AA was significantly reduced.