Changing renin substrates in human pregnancy.

Renin substrate of high molecular weight was identified in plasma from pregnant women, non-pregnant subjects and in samples of umbilical arterial and venous plasma, using gel filtration chromatography. The proportion existing in the high molecular weight form in pregnant women was significantly increased above that of non-pregnant subjects by 11 weeks after the last menstrual period and continued to rise to term. In contrast, the proportion in fetal plasma was significantly lower than that of the non-pregnant group. High molecular weight renin substrate was itself heterogeneous and appeared to consist of four sub-groups. In non-pregnant adults the first peak, eluting near the void volume of the column, was the largest. In the fetus this profile was reversed. The elution profile in maternal plasma had changed markedly by as early as 8 weeks of gestation. Thereafter, it was possible to see increasing dominance of the minor 'intermediate' peaks visible in the non-pregnant adult until, in the third trimester, the high molecular weight form was eluted as a large broad band with little evidence of the individual peaks. Oestrogens are the most likely stimulus for the increased production of the high molecular weight renin substrate in pregnant women. In the fetus, although the same form of renin substrate is stimulated, the actual amount in the high molecular weight range is very small. This may be because oestrogens are sulphated in the fetus or because the fetal liver is not very responsive to the stimulation. The similarity between the profiles of mother and fetus may indicate a common source of production of renin substrate in the feto-placental unit.

The effect of changes in blood gas tension upon the renin-angiotensin system of the newborn infant.

Renin and renin-substrate concentrations were measured in the paired umbilical artery and vein blood of 20 babies born by elective caesarean section, and 36 babies born vaginally. Blood pH, carbon dioxide tension and oxygen tension were measured in all samples. Babies born vaginally were significantly more acidaemic than those delivered by caesarean section. The cord artery blood also had a significantly greater carbon dioxide tension at vaginal delivery. A decrease in pH of either cord artery or vein blood, irrespective of mode of delivery, was associated with an increase in renin concentration. Renin-substrate concentration tended to be lower in the cord vein blood of acidaemic babies born vaginally, such that the ratio renin: renin-substrate concentration was negatively correlated with pH. At caesarean section the renin concentration of cord vein blood was positively correlated with carbon dioxide tension and increased dramatically at oxygen tensions less than 3kPa. This was not observed in babies born vaginally, but the cord artery substrate concentration in these infants was positively correlated with carbon dioxide tension. Thus changes in the renin-angiotensin system at birth may partly be affected by blood gas tension.

Studies on the effect of mode of delivery on the renin-angiotensin system in mother and fetus at term.

Plasma renin substrate (PRS) and renin (PRC) concentrations were measured in the paired umbilical artery and vein blood of 54 babies and in the venous blood of 23 of their mothers at vaginal delivery. Similar samples were collected from 31 babies and their mothers at elective caesarean section. Fetal renin concentrations in both umbilical artery and vein blood were markedly increased at vaginal delivery compared with values at operative delivery. Renin substrate concentration was correlated with the length of second stage of labour. Umbilical vein PRC and PRS were greater than corresponding umbilical artery values at vaginal, but not at operative delivery, suggesting that some factor associated with delivery might stimulate the placenta to produce renin and renin substrate during vaginal delivery. Maternal and umbilical concentrations of both renin and renin substrate were unrelated, supporting the view that the maternal and fetal compartments are independent. It is suggested that hyperactivity of the renin-angiotensin system may be an integral part of the marked changes in cardiovascular homeostasis which occur at birth.