In fetal and adult mammals the neurohypophysial peptide arginine vasopressin (AVP) is secreted in response to similar osmotic and volume stimuli. In the fetus, AVP and arginine vasotocin (AVT) are physiologically important in the regulation of fetal lung fluid secretion and renal free water and sodium excretion. In adult mammals, the effects of the recently characterized atrial natriuretic peptide (ANP) on renal water and sodium excretion are, in general, opposite to the actions of AVP. However, the involvement of ANP in fetal renal function has not been investigated. The proposed studies have been designed to characterize the ontogenesis of AVP and/or AVT receptors, to define the secretion, metabolism and function(s) of ANP in the fetus and newborn, and to study the counter-regulatory actions of AVP and ANP on fetal water and salt metabolism and renal function. Initially, AVP and AVT actions in vivo will be differentiated on the basis of specific receptors (V1, V2 or AVT) by use of specific V1 and V2 receptor agonists and antagonists. In vitro studies will be performed to characterize the tissue distribution (renal, vascular, pulmonary and placenta) of AVP/AVT receptors and to quantify the ontogeny of receptor specificity and binding capacity, i.e., does fetal receptor maturation entail a transition from primarily AVT receptors to a population of AVP specific receptors. Subsequently, the ovine ANP will be isolated and in vivo studies of fetal, newborn and adult ANP secretion, metabolism and physiologic actions performed so that AVP and ANP physiologic effects may be compared. ANP receptor ontogeny also will be characterized in vitro. Finally, the counter-regulatory actions of AVP and ANP in terms of secretion and function will be investigated, both in vivo and in vitro. Chronically catheterized fetal, newborn and adult sheep will be the primary in vivo experimental models.
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