The goal of this proposal is to examine the adaptation of the developing kidney and related vasoactive mediator sytems to chronic intrauterine hypoxia in the maintenance of homeostasis before and immediately following birth. We also plan to investigate the modulation of these systems by renal prostaglandins in the process of maturation and adaptation to asphyxial stress, parturition and extrauterine life. For this purpose we propose to study the renal function in the lamb in relation to vasopressin, catecholamines, renin-angiotensin system and protaglandins during the third trimester and first week of life under the following conditions: a) Normal gestation - term delivery, b) Normal gestation - preterm delivery, c) placental insufficiency and d) Deranged maternal environment. The fetal kidney is relatively "dormant" playing only a minor role is maintaining fluid and electrolyte balance in utero. Nevertheless, the developing kidney is unique in that while it is involved in preserving cardiovascular homeostasis, through the renin-angiotensin system, it can also be adversely affected by the cardiovascular and endocrine responses to asphyxia. Our current work on the fetal lamb has shown that during acute hypoxic stress, there is a reduction in GFR and excessive excretion of fluid and electrolytes. These changes in renal function are related to the stimulation of vasoactive mediators and are reversible provided the insult is not too severe and is of short duration. Because many aspects of renal function can be measured in utero, the fetal kidney can serve as a model for the study of the effects of a variety of stimuli on an organ system which is relatively "dormant" and plays a minor role in homeostasis until birth.