11-BETA-HYDROXYSTEROID DEHYDROGENASE AND ITS INHIBITORS IN HYPERTENSIVE PREGNANCY

Preeclampsia is accompanied by amplification of the sodium retention t hat is a feature of normal pregnancy. Recent evidence suggests that mi neralocorticoid receptor activation is increased in preeclampsia, but classic mineralocorticoids (aldosterone, 11-deoxycorticosterone) are n ot present in excess. Cortisol can act as a mineralocorticoid receptor agonist only when its renal inactivation to cortisone by 11 beta-hydr oxysteroid dehydrogenase is impaired, for example, in congenital enzym e deficiency and after administration of exogenous inhibitors (eg, lic orice). Endogenous inhibitors of this enzyme have been detected in hum an urine and are increased in pregnancy. To establish whether cortisol causes mineralocorticoid excess in hypertensive pregnancy and whether endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase are res ponsible, we studied 25 hypertensive pregnant patients (13 with preecl ampsia and 12 with gestational hypertension), 16 normotensive pregnant subjects, and 13 nonpregnant control subjects. Concentrations of plas ma renin and aldosterone were increased in pregnancy, but less so in h ypertensive pregnancy. Plasma potassium and urinary electrolytes were not different between the groups. Plasma cortisol was increased in pre gnancy but not different in hypertensive pregnancy, and urinary cortis ol, plasma and urinary cortisone, acid urinary tetrahydrocortisol and tetrahydrocortisone were not different between the groups. Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase were more active in urine from pregnant women but were not increased further in hypertens ive pregnancy. There were no differences in these parameters between p atients with preeclampsia and gestational hypertension. We conclude th at deficient inactivation of cortisol to cortisone does not contribute to the sodium retention of normotensive or hypertensive pregnancy and that endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase ha ve no evident pathophysiological significance in pregnancy.