Sodium and mineralocorticoids in normal pregnancy

For many years clinicians have speculated that abnormal sodium metabolism plays an important role in the pathogenesis of hypertension. This consideration probably has been most evident in obstetrical practices directed toward preventing hypertensive disorders of pregnancy. It was commonly assumed that normal gestation was associated with sodium-retaining tendencies, which were thought to be causally related to the development of preeclampsia. Accordingly, pregnant women customarily were treated as though threatened by excessive sodium retention; dietary salt restriction and diuretics were prescribed routinely as precautionary measures. In view of this concern, it is quite understandable that the discovery of aldosterone and the recognition of its causal relationship to hypertension in Conn's syndrome quickly led early investigators to study the possible pathogenic role of this potent mineralocorticoid in the hypertensive disorders of pregnancy. Initial reports suggesting that aldosterone levels were higher in preeclamptic than in nonpregnant women generated considerable excitement, which quickly was tempered by the observation that aldosterone secretion was increased to an even greater extent in normal gravidas [1]. Since then, results of numerous studies have provided confirmation that aldosterone levels are markedly elevated in normal gravidas compared with nonpregnant women on similar salt intakes [2, 3]. More recently, it has been shown that secretion of another potent mineralocorticoid, desoxycorticosterone, also is increased substantially during normal pregnancy [4, 5]. Nonetheless, normal gravidas do not demonstrate clinical evidence of mineralocorticoid excess, and the blood pressure falls below pregnancy values during the first two trimesters. Although the regulation of aldosterone secretion in pregnancy has been studied extensively, the physiologic significance of the markedly increased secretion of aldosterone remains controversial. There is considerable evidence that normal pregnancy results in a tendency towards a reduced effective blood volume, despite the high levels not only of aldosterone and desoxycorticosterone, but also of estrogens, which have sodium-retaining effects in man. Thus, some propose that the enhanced secretion of aldosterone is a compensatory response required to maintain normal volume homeostasis [6]. Others argue that the augmented extracellular and intravascular fluid volumes measured in normal pregnancy, as well as the accompanying rise in cardiac output and in the GFR, are inconsistent with functional hypovolemia, and suggest that these changes more likely reflect sodium retention induced by aldosterone hypersecretion [7]. Questions regarding the role of increased aldosterone in pregnancy, whether it is associated with a tendency to lose or to retain sodium, not only have a bearing upon routine management of pregnant women, but are also of fundamental importance to our understanding of the pathophysiology of the gestational hypertensive disorders. In attempting to resolve these issues, it would seem appropriate to review studies that might help to define the role of increased mineralocorticoids in normal pregnancy.