Ontogeny of the Renin-Angiotensin-Aldosterone System in the Fetal and Newborn Lamb

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Abstract
Summary: Thirteen chronic fetal Iamb preparations between 95 and 142 days of gestation (term 145–150 days), and 10 newborn lambs were studied before and after the acute (1–2 min) infusion of furosemide (2 mg/kg). The baseline to peak plasma renin activity (PRA) response to furosemide increased from A 3.0 ± 1.3 ng/ml/hr (M and SEM) and 95–106 days of gestation to Δ 18.4 ± 4.0 (P < 0.01) at 123–142 days and Δ 33.6 ± 6.5 (P < 0.001) in the newborn. Baseline plasma aldosterone concentrations were similar in the fetus and pregnant ewe; aldosterone levels were higher in the newborn lamb than in the nonpregnant ewe. The newborn plasma aldosterone response to furosemide via the endogenous rennin-angiotensin system was Δ 17.1 ± 4.2 ng/dl (P < 0.01); the fetal lamb plasma aldosterone level did not increase. The results indicate that the renin-angiotensin system cannot be stimulated by furosemide under 106 days of gestation; the response after 110 days increases with gestational age. Aldosterone concentrations in the fetal lamb are probably maintained primarily by the pregnant ewe and do not increase in response to endogenous renin stimulation as in the newborn. Speculation: Fetal renin responsiveness increases with gestational age, while fetal aldosterone secretion is unresponsive to stimulation by the renin-angiotensin system. Therefore, the fetal adrenal cortex is the limiting factor in the pituitary-renal-adrenal axis before term.

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