IMPAIRED RENIN STIMULATION IN PREECLAMPSIA

1. Pre-eclampsia is characterized by reduced plasma active renin conce ntration and renal prostacyclin production. The aim of this study was to determine whether the plasma active renin concentration could be st imulated in women with pre-eclampsia by intravenous frusemide, which s timulates renin acutely through a prostacyclin-mediated mechanism. 2. Plasma active renin concentration, plasma aldosterone concentration, h aematocrit and urinary sodium, creatinine and 6-keto-prostaglandin F-1 alpha were measured before (0) and 15, 30 and 60 min after intravenou s frusemide in 10 non-pregnant women, 10 normal pregnant women and nin e women with preeclampsia. Six normal pregnant and six non-pregnant wo men underwent the same measurements after injection of 2ml of saline t o control for effects of time and posture. 3. Baseline plasma active r enin concentration (but not plasma aldosterone concentration) was lowe r 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 u rinary 6-keto-prostaglandin F-1 alpha/creatinine ratio, urinary sodium excretion and fractional sodium excretion did not differ between norm al pregnant and pre-eclamptic women. 4. After frusemide, plasma active renin concentration rose significantly in non-pregnant (P = 0.002) an d normal pregnant (P = 0.008) women, but not in women with pre-eclamps ia. Individual results showed stimulation in all non-pregnant and norm al pregnant women but in only six out of nine pre-eclamptic women, sig nificantly fewer than in normal pregnancy (P < 0.05). The overall magn itude of the response of plasma active renin concentration to frusemid e was blunted significantly in pre-eclamptic compared with normal preg nant women (P = 0.022).5. Absolute and fractional sodium excretion and haematocrit rose significantly in all groups and the magnitude of cha nge did not differ among groups for any of these parameters. The urina ry 6-ketoprostaglandin F-1 alpha/creatinine ratio increased significan tly only in non-pregnant women (P = 0.01), with variable individual re sponses in normal and hypertensive pregnant women. 6. This study shows that normal pregnant women exhibit natriuresis and stimulation of pla sma renin after frusemide similar to that of non-pregnant women. Howev er, pre-eclamptic women, as a group, have impaired renin stimulation a fter frusemide but a similar natriuresis to that of normal pregnant wo men. The mechanisms of these changes are unclear but are consistent wi th the notion of 'exhausted' renal renin in some women with pre-eclamp sia.