The objective of the proposed project will be to provide information regarding the maturation and function of a renin-angiotensin-mineralocorticoid system in the sheep fetus and newborn lamb. This information may have relevance to development of fluid and electrolyte therapy schedules for normal and sick preterm human infants. There are three main modulators of aldosterone secretion: ACTH, potassium levels, and the renin angiotensin system. The studies in the present grant will utilize the chronic fetal sheep preparation to study the maturation and function of the renin-angiotensin-aldosterone system in the fetus and in the newborn lamb. The studies will involve stimulation and inhibition of the renin-angiotensin and aldosterone system using furosemide, changes in blood volume and pressure, changes in potassium level, and by assessing the response to salt loading. In addition, certain anatomic and functional maturation studies of the juxtaglomerular apparatus will be performed. The control of the renin-angiotensin-aldosterone system will be studied by using blocking agents for both adrenergic alpha and beta receptors and the effect of various modes of birth. In addition, amniotic fluid metabolism will be studied in relationship to plasma renin activity, salt loading, and sodium restriction.