1. In a prospective study involving fifty-six women, measurements of body weight, urinary creatinine, sodium and potassium and plasma sodium, potassium and renin activity were made in mid-pregnancy and at 36 weeks. The effect of sodium restriction and sodium loading on these measurements was assessed in mid-pregnancy.
2. Mean plasma renin activity was significantly higher throughout pregnancy than the normal non-pregnant mean level. It was lower at 36 weeks than in mid-pregnancy in those whose pregnancy was normal but not in those who developed toxaemia of pregnancy between 38 and 40 weeks. In mid-pregnancy in both groups sodium depletion was significantly elevated but sodium loading did not significantly depress plasma renin activity.
3. The urinary potassium/creatinine ratio in mid-pregnancy and urinary sodium/creatinine ratio at 36 weeks were lower in those who subsequently developed toxaemia, raising the possibility of a functional renal lesion which antedates the morphologically recognizable lesion of late pregnancy.
4. In a second study involving sixty-six different women plasma angiotensin II levels between 6 and 40 weeks of pregnancy were mostly above the normal range, and highest levels were observed between 21 and 30 weeks. The plasma angiotensin II levels in six women with established toxaemia of pregnancy were not significantly different from the levels in nine women with normal pregnancy of the same duration.
5. While the renal glomerular lesion is presumably the major determinant in the development of toxaemia, the heightened activity of the renin-angiotensin-aldosterone system which is appropriate to normal pregnancy is an aggravating factor in established toxaemia, and may predispose to its development in some patients by failing to decline in late pregnancy.