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In a study of 38 fetuses total kidney renin was significantly correlated with gestational age (r=0.63). Although whole fetal kidney renin specific activity was found to decrease with gestational age (r=–0.65), the mean value of the specific activity was about 20 times greater than in normal adult cortex and double that in tissue from patients with renal artery stenosis, suggesting renin-angiotensin system hyperactivity.In approximately 40% of fetal kidneys examined, evidence for an inactive (trypsin-activatable) renin precursor was found. The molecular weight of this form was indistinguishable from active renin (45 000 daltons) by Sephadex chromatography.Amniotic fluid from nine cases (100%) contained angiotensin (ANG) I, angiotensin converting enzyme (ACE), renin substrate, active and inactive renin (both 45 000 daltons).Five of the 38 (13%) fetal adrenal glands contained renin, but no evidence for trypsin-activatable forms. Aldosterone was present in low concentration in the earliest adrenals examined, and a positive correlation existed between total tissue aldosterone and gestational age (r=0.73).These findings suggest that the fetal renin-angiotensin system has an important role to play in the maintenance of extracellular fluid volume and blood pressure in the developing fetus.