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.