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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)

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 effect of doubling doses of angiotensin II on maternal systemic blood pressure and arcuate and fetal umbilical artery Doppler velocity profiles has been investigated in 10 women in first- and 10 in second-trimester pregnancy. Ten non-pregnant women were also studied. 2. A progressive decrease in the pressor response to angiotensin II in early pregnancy as previously described was confirmed. 3. Angiotensin II induced a significant dose-dependent increase in the pulsatility index (a measure of downstream resistance) in the umbilical artery in both first- and second-trimester patients. There was an apparent increase in the threshold response of the pulsatility index to angiotensin II in the umbilical artery as pregnancy progressed. There was also a significant correlation between changes in maternal systolic or diastolic pressure and change in umbilical artery pulsatility index, but this did not differ between the two trimesters. This suggests that the increase in pulsatility index is related to blood pressure rather than angiotensin II. This is consistent with reports that angiotensin II does not cross the haemomonochorial placenta. 4. Basal pulsatility index in the arcuate artery fell with increasing gestation. There was a significant inverse association between the evoked change in maternal systemic blood pressure and the change in arcuate artery pulsatility index, suggesting local vasodilatation. 5. We conclude that acutely increasing maternal blood pressure leads to increased vascular resistance on the fetal side of the circulation.

1. A radioimmunoassay for the measurement of angiotensin II in 1 ml of plasma has been developed and used to measure angiotensin II in maternal peripheral, cord venous and cord arterial blood in 45 patients at delivery. 2. In babies delivered vaginally, cord venous and cord arterial concentrations of angiotensin II were significantly higher than maternal venous blood concentrations. There was a significant relationship between both cord venous and cord arterial concentrations and maternal concentrations of angiotensin II. 3. Cord venous concentrations of angiotensin II were significantly greater than those in cord arterial blood in babies delivered vaginally but not in those delivered by lower-segment Caesarean section. This suggests the possibility that, during labour, the placenta may contribute to foetal concentrations of angiotensin II. 4. Maternal and cord venous concentrations of angiotensin II were significantly higher in patients with hypertensive disease of pregnancy than in those who had remained normotensive throughout pregnancy. 5. Cord venous concentrations of angiotensin II increased significantly with increasing duration of the second stage of labour.

Plasma renin and angiotensin II levels were measured in nine patients immediately before and at half-hourly intervals in the four hours following therapeutic termination of pregnancy. There was a small fall in renin and angiotensin II levels over the first 1 to 2 hours, followed by a slight increase. The magnitude of these effects was much smaller than those previously seen following normal delivery. It is concluded that in early pregnancy maternal, rather than feto-placental, factors are controlling the renin-angiotensin system.

Factors which influence levels of plasma AII in late pregnancy have been studied in 50 primigravidas and 53 multigravidas. A highly significant relationship has been shown between diastolic blood pressure and plasma AII (r = 0.4190 p less than 0.005) in primigravidas but not in multigravidas (r = 0.205; p less than 0.3). Multiple regression analysis and analysis of covariance have been applied to a series of independent variables with plasma AII as the dependent variable. The single most important variable related to AII levels in primigravidas was diastolic blood pressure whereas in multigravidas it was proteinuria. Rhesus blood group was shown to have a significant effect in both parity groups, Rh-negative primigravid women exhibiting higher values of AII.

Concentrations of plasma angiotensin II (AII) have been measured in the second stage of labour or before delivery by elective Caesarean section in 134 women and some factors influencing the levels have been assessed. Plasma AII concentrations in the second stage of labour were higher than levels previously observed before the onset of labour in both primigravid and multiparous women. Markedly lower levels were found following delivery by elective Caesarean section than following vaginal delivery. Multiparae had higher AII concentrations than primigravidae both before the onset of labour and at delivery. Epidural analgesia was associated with significantly lower AII concentrations; in primigravidae receiving such analgesia a statistically significant relation was found between AII concentration and diastolic blood pressure at delivery. A similar relation was found in the nonproteinuric patients delivered by Caesarean section. The estimated duration of the second stage of labour was the major factor affecting AII concentration in normal multiparae. In both primigravid and multiparous women, AII concentrations were markedly raised in association with proteinuria.

Plasma renin activity, plasma renin concentration and plasma angiotensin II were measured in 18 primigravid women and 17 multiparous women between 37 and 42 weeks of gestation. Seven of the primigravid and seven of the multiparous women were admitted to hospital because they developed hypertension during pregnancy. In the primigravid group, the mean angiotensin II level was significantly higher in the hypertensive than in the normotensive women. A highly significant correlation was found between diastolic blood pressure and plasma angiotensin II levels. Although a similar trend was seen in the multiparous women, there was a wide scatter of values and the relationship between diastolic blood pressure and plasma angiotensin II was not significant. No correlation could be established between plasma renin concentration and angiotensin II levels. However, there was a trend towards a negative correlation between plasma renin activity and plasma angiotensin II, suggesting that high angiotensin levels may suppress renal renin release. The influence of parturition on plasma angiotensin II levels was investigated in 12 women. Maternal plasma angiotensin II levels were significantly higher in the second stage of labor than in women delivered by elective cesarean section.

Twelve women in their first 3 months of pregnancy received an i.v. saline load (3 mmol sodium/kg) and a graded infusion of angiotensin II (Ang II; i.e. 4, 8 and 16 ng/kg per min). As controls, twelve comparable pregnant subjects received the saline infusion alone. Eight non-pregnant women underwent both protocols, with doses of 2, 4 and 8 ng/kg per min Ang II, and thus acted as their own controls. Saline loading evoked proportionately similar falls in basal plasma renin (PRC) and plasma aldosterone (PAC) concentrations in pregnant and non-pregnant women. Angiotensin II evoked a dose-dependent pressor response, a graded increase in PAC and a reduction in sodium and urate excretion in both pregnant and non-pregnant women. The administration of Ang II had a proportionately greater effect on sodium and urate excretion in non-pregnant than in pregnant women; the pressor response to Ang II was also decreased in the pregnant women. The stimulation of PAC by Ang II, however, did not differ between the two groups. These results show that refractoriness to the renal and vascular effects of Ang II is present as early as the eleventh week of gestation. They also support the hypothesis that there is a degree of dissociation between the renin-angiotensin system and PAC in normal pregnancy.

Plasma angiotensin II was measured in the umbilical cord arterial and/or venous blood of 54 babies delivered vaginally and in 12 delivered by elective lower segment cesarean section. Angiotensin II was also measured in the peripheral venous blood of 51 of the mothers. Mean angiotensin II levels at delivery were higher in the cord venous blood of infants born to hypertensive than to normotensive mothers. Cord venous angiotensin II levels were always higher than those of the mother and there was a strongly positive relationship between maternal and fetal angiotensin II. The duration of the second stage of labor was found significantly to affect fetal angiotensin II levels, prolonged labor being associated with high levels. When this was taken into account, there was a highly significant positive relationship between the body weight of the infants and cord venous angiotensin II levels. There was an inverse relationship between cord venous pH and angiotensin II levels. Babies delivered by lower segment cesarean section had much lower angiotensin II levels than those delivered vaginally. The levels were, however, twice as high as those in the nonpregnant adult.

The renin-angiotensin system shows a marked increase in activity in normal pregnancy, with the major changes occurring in the first trimester. Evidence is presented to show that there is a physiologically inactive prorenin present in the plasma during pregnancy that achieves highest levels in the first half of pregnancy. The significance of this "acid-activated" renin has yet to be determined. Plasma angiotensin II levels are elevated throughout normal pregnancy, and a significant positive relationship has been established between maternal venous and cord venous levels at delivery. Recent studies on plasma AII levels in pregnancy hypertension have shown a positive correlation between diastolic blood pressure and plasma AII, and there is evidence that the high circulating levels of angiotensin may result in a feed-back suppression of renal renin release. Studies on the fetal circulation at delivery have also shown high levels of AII in the cord venous blood of infants born to mothers with pregnancy hypertension. Despite the increased level of activity of the renin-angiotensin system in normal pregnancy, sodium homeostasis is maintained. The possible reasons for the increased activity are discussed briefly.

The binding of tritiated angiotensin II to 20,000 x g particulate tractions of human placenta, chorion, and amnion was investigated. Binding to particles from the three tissues reached equilibrium within 10 minutes at 29 degrees C and was displaced by the addition of 1,000-fold excess of unlabeled angiotensin II. Scatchard analysis of the data showed that two classes of binding sites were present in the placental preparation. For the high-affinity site, values of 9 x 10(-9) M and 300 fmoles/mg of protein were obtained for the dissociation constant and the binding capacity, respectively. There was little specific binding in chorion and amnion.

Plasma renin activity and concentration and angiotensin II concentration have been measured serially in six normotensive primigravidae and in four mildly hypertensive patients in the four immediately following normal delivery. In normotensive patients, both renin and angiotensin II levels fell sharply over the first two hours to levels within the non-pregnant range, with a subsequent rise to levels, similar to those found in late pregnancy. Changes in the mildly hypertensive patients were smaller, and somewhat slower. It is suggested that the initial fall represents clearance of a renin of fetoplacental origin and that the subsequent rise may be a release from feedback suppression of renal renin synthesis.

Plasma renin concentration, renin activity and angiotensin II (AII) have been studied in 35 primigravidae at or near term immediately prior to surgical induction of labour. A highly significant positive correlation was established between diastolic blood pressure at the time of sample collection and plasma AII. This relationship was observed over the range of diastolic pressure studied irrespective of the diagnosis made at the time of admission to hospital. In patients with hypertension, a significant negative relationship was established between plasma renin concentration and renin activity and AII. Furthermore, plasma AII levels were higher for a given plasma renin activity or plasma renin concentration in the hypertensive women than in the normotensive group. These findings suggest that the renin-angiotensin system is actively involved in hypertensive disease of pregnancy and that suppressed levels of renin concentration and activity may result from elevated angiotensin levels. It is suggested that the utero-placental complex may be the source of the elevated AII levels.