Impaired Renin Stimulation in Pre-Eclampsia

Abstract

1. Pre-eclampsia is characterized by reduced plasma active renin concentration and renal prostacyclin production. The aim of this study was to determine whether the plasma active renin concentration could be stimulated in women with pre-eclampsia by intravenous frusemide, which stimulates renin acutely through a prostacyclin-mediated mechanism. 2. Plasma active renin concentration, plasma aldosterone concentration, haematocrit and urinary sodium, creatinine and 6-keto-prostaglandin F1α were measured before (0) and 15, 30 and 60 min after intravenous frusemide in 10 non-pregnant women, 10 normal pregnant women and nine women with pre-eclampsia. Six normal pregnant and six non-pregnant women underwent the same measurements after injection of 2ml of saline to control for effects of time and posture. 3. Baseline plasma active renin concentration (but not plasma aldosterone concentration) was lower in pre-eclamptic women [4.0 (1.7–6.2) pmol of angiotensin I h−1 ml−1; median (interquartile range)] than in normal pregnant women [6.7 (5.3–12.2) pmol of angiotensin I h−1 ml−1] (P < 0.05). Baseline urinary 6-keto-prostaglandin F1α/creatinine ratio, urinary sodium excretion and fractional sodium excretion did not differ between normal pregnant and pre-eclamptic women. 4. After frusemide, plasma active renin concentration rose significantly in non-pregnant (P = 0.002) and normal pregnant (P = 0.008) women, but not in women with pre-eclampsia. Individual results showed stimulation in all non-pregnant and normal pregnant women but in only six out of nine pre-eclamptic women, significantly fewer than in normal pregnancy (P < 0.05). The overall magnitude of the response of plasma active renin concentration to frusemide was blunted significantly in pre-eclamptic compared with normal pregnant women (P = 0.022). 5. Absolute and fractional sodium excretion and haematocrit rose significantly in all groups and the magnitude of change did not differ among groups for any of these parameters. The urinary 6-keto-prostaglandin F1α/creatinine ratio increased significantly only in non-pregnant women (P = 0.01), with variable individual responses in normal and hypertensive pregnant women. 6. This study shows that normal pregnant women exhibit natriuresis and stimulation of plasma renin after frusemide similar to that of non-pregnant women. However, pre-eclamptic women, as a group, have impaired renin stimulation after frusemide but a similar natriuresis to that of normal pregnant women. The mechanisms of these changes are unclear but are consistent with the notion of ‘exhausted’ renal renin in some women with pre-eclampsia.