MOLECULAR, CELLULAR & PHYSIOLOGICAL CONTROL OF RENAL FUNCTION DURING DEVELOPMENT

尿钠排泄增加的机制 胎儿生命和早产儿的风险尚未得到仔细阐明。 最近的研究表明，不成熟的能力的变化， 肾脏重吸收钠的能力直接依赖于 几种膜转运蛋白。 研究旨在 研究分子、细胞和生理机制 调节离子通过肾小管转运的发展 膜在胎儿的生活和过渡期间，从胎儿到 新生的生命更具体地说，我们建议测试一般 肾小管细胞发育分化假说 是与重要的变化，在功能和丰富的 作为交换器、泵或通道的膜蛋白， 允许离子穿过管状膜传输，并 确定影响胎儿生命期间这些变化的因素， 从胎儿到新生儿的过渡期。为了考验这位将军 假设，本建议的目的是a）阐明肾 Na +/H+交换器、Cl-/碱交换器和Na +/K +-ATP酶的成熟 从胎儿到新生儿过渡期间的活动，并确定是否 Na~+/H~+交换器的成熟先于Na~+/K~+-ATP酶的升高 在从胎儿到新生儿的过渡期间的活性; B）测试 假设糖皮质激素和甲状腺激素在 在Na +/H+交换器、Cl-/碱交换器的肾成熟中的作用， 胎儿和出生后发育过程中Na+，K +-ATP酶活性的变化及其与胎儿发育的关系 确定这两种激素是否对近端 管状离子转运; c）检验甲状腺切除术 阻止或延迟近端小管离子转运的出生后成熟; 以及d）检验早产绵羊的不敏感性 胎儿近曲小管离子转运机制对血管紧张素II的影响 继发于血管紧张素受体饱和。

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.