Factors Controlling Aldosterone Secretion during Hypoxemia in Fetal Lambs

Abstract

SummaryFactors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 2 0.1 meqtliter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P < 0.001) and with changes in plasma angiotensin I1 concentration ( r = 0.77; P < 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ ( r = 0.79; P < 0.001) but not with plasma angiotensin I1 values ( r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery ( r = 0.36; P > 0.1) in captopriltreated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus. It is also suggested that maternal placental transfer of aldosterone is not an important factor controlling the rise in fetal plasma aldosterone concentration during hypoxemia.Abbreviations A-11, angiotensin I1 ACTH, adrenocorticotrophin PRA, plasma renin activity Much has been learned about the direct mediators governing aldosterone secretion in adult humans and experimental animals ( 14, 18). However, mechanisms regulating aldosterone secretion during fetal life are poorly understood. Previous in vitro studies (3, 8,20,32,33) have shown that the fetal adrenal gland has the ability to synthesize and secrete aldosterone following stimulation by either A-I1 (33), ACTH (33), or increasing potassium concentration (32). More recently, we (2 1, 22) and others (27) demonstrated that in vivo elevation of plasma A-I1 concentration stimulates aldosterone secretion during the last trimester of gestation in fetal lambs but to a lesser degree than in adult ewes (22). However, in vivo attempts to stimulate aldosterone secretion by ACTH (1, 5 ) or potassium infusion (3 1) have been unsuccessful, suggesting a relative insensitivity of the fetal adrenal to these stimuli.On the other hand, we have found a close correlation between plasma aldosterone and plasma potassium concentrations iia nephrectomized fetuses submitted to blood volume depletion (21). Similar findings have also be...

Transient elevation of aldosterone levels in perinatal asphyxia

“…Although there was an association between fetal acidemia and high potassium levels in cord blood, there was no correlation between aldosterone and potassium levels, suggesting that umbilical cord aldosterone concentrations are not related to potassium levels. This finding confirms fetal lamb studies which showed that the rise in plasma aldosterone levels during hypoxemia is not related to activity of renin-angiotensin system or to high potassium levels (13).…”

Is the Fetal Lung a Mineralocorticoid Receptor Target Organ? Induction of Cortisol-Regulated Genes in the Ovine Fetal Lung, Kidney and Small Intestine

“…Relatively low 11β-HSD2 expression in the late gestation fetal lung would allow binding of circulating cortisol to MR in the fetal lung even in unstressed fetuses before term; free cortisol levels in the ovine fetus at 120–130 days of gestation are estimated to be 1–2 n M , within the range for binding at ovine or human MR (ovine MR: K i 0.2 n M , K d 0.5 n M [38]; human MR: K i 0.13 n M [39]). Moreover, fetal cortisol levels are approximately 20-fold higher than those of aldosterone in the unstressed fetus, suggesting that cortisol is likely to be the sole ligand at MR in 11β-HSD2 deficient tissues prior to term, except in conditions of fetal hypoxia in which aldosterone would be increased sufficiently to also bind appreciably at MR [40]. In guinea pig fetal lungs, treatment with aldosterone has been shown to significantly decrease the rate of lung fluid production [41], indicating a role of MR in reabsorption in that species.…”

Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep

“…The release of renin from the ovine kidney occurs even at this very young age (0.6 gestation) in response to hypotension caused by hemorrhage (9). Hypoxia is known to be only a weak-to-modest stimulus to renin and ANG II production in the fetus (8,17,25,31); however, there have been no studies of the effects of asphyxia on the fetal RAS. From this literature, we hypothesized that the development of hydrops fetalis after asphyxia in the 0.6 gestation sheep fetus would be associated with activation of the fetal RAS.…”