Role of cortisol in the ontogenic control of pulmonary and renal angiotensin-converting enzyme in fetal sheep near term

1. This study examined the ontogeny of angiotensin-converting enzyme (ACE) concentration in the lungs and kidneys of fetal, newborn and adult sheep, a nd investigated the effects of cortisol infusion on tissue and plasma ACE i n the chronically catheterised ovine fetus. 2. Pulmonary and renal ACE in utero increased from 113 days of gestation to wards term; peak tissue ACE concentrations were observed in fetuses studied at 143 da;vs (term, 145 +/- 2 days). The high level of ACE seen in the fet al lungs close to term was maintained in the lambs and adult ewes whereas r enal ACE decreased immediately after birth and rose to a maximal value in t he adult ewes. In all groups of animals studied, higher mean concentrations of ACE were observed in the kidneys than in the lungs. Ontogenic increment s in pulmonary and renal ACE in utero were coincident with the prepartum co rtisol surge. In untreated and saline-infused fetuses, plasma cortisol corr elated with both pulmonary (r = 0.83, P < 00001) and renal (r = 0.53, P < 0 .01) ACE concentrations, irrespective of gestational age. 3. An intravenous infusion of cortisol (2-3 mg kg(-1) day(-1)) at either 11 3 or 129 days raised plasma cortisol to the level seen near term and caused an increase in pulmonary ACE at both gestational ages. Pulmonary ACE conce ntration in the cortisol-infused fetuses at 129 days, but not at 113 days, was similar to that observed in the fetuses near term. In contrast, cortiso l infusion had no effect on renal ACE concentration at either 113 or 129 da ys of gestation. Plasma ACE concentration was also increased by exogenous c ortisol at 129 days. 4. Therefore, these findings suggest that the ontogenic rise in BCE concent ration observed in the lungs of the sheep fetus near term is induced, at le ast in part, by the prepartum cortisol surge.