The mechanisms responsible for the high urinary sodium excretion during fetal life and in pre-term infants have not been carefully elucidated. Recent studies have suggested that changes in the ability of the immature kidney to reabsorb sodium are directly dependent on the development of several membrane-transporting proteins. Studies are designed to investigate the molecular, cellular, and physiological mechanisms regulating the development of ion transport across the renal tubular membranes during fetal life and during the transition from fetal to newborn life. More specifically, we are proposing to test the general hypothesis that the developmental differentiation of renal tubular cells is associated with important changes in the function and abundance of membrane proteins that function as exchangers, pumps, or channels and allow for the transport of ions across the tubular membranes, and to determine the factors influencing these changes during fetal life and during the transition from fetal to newborn life. To test this general hypothesis, the present proposal is designed a) to elucidate the renal maturation of Na+/H+ exchanger, Cl-/base exchanger, and Na+/K+-ATPase activity during the transition from fetus to newborn, and to determine if the maturation of Na+/H+ exchanger precedes the rise in Na+/K+-ATPase activity during the transition from fetus to newborn; b) to test the hypothesis that glucocorticoids and thyroid hormones play an important role in the renal maturation of Na+/H+ exchanger, Cl-/base exchanger, and Na+,K+-ATPase activity during fetal and postnatal development and to determine if there is synergistic action of these two hormones on proximal tubular ion transport; c) to test the hypothesis that thyroidectomy prevents or delays postnatal maturation in proximal tubular ion transport; and d) to test the hypothesis that the insensitivity of the pre-term sheep fetus proximal tubule ion transport mechanisms to angiotensin II is secondary to saturation of angiotensin receptors.
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