ONTOGENESIS OF THE SYMPATHETIC CONTROL OF RENAL FUNCTION

本建议的总体目标是研究在正常和 病理条件下，交感神经系统的作用，在调节 肾血流动力学和肾功能在发展过程中使用慢性 插管和清醒的胎儿，新生儿和成年羊。 （一）第一 这项建议的主要目的是检验以下假设： 肾血流动力学和功能对α、β和多巴胺的反应 受体刺激在胎儿、新生儿和成年动物之间不同。 更 具体而言，该建议旨在研究肾功能的能力， α、β和多巴胺能受体（a）调节肾血管 张力，和（B）肾小球滤过率、钠和水代谢，和 在发育过程中释放肾素。 肾内输注不同的α， 将使用β和多巴胺激动剂和拮抗剂。 此外，（c） 这些体内实验的结果将与体外实验结果相关联。 胎儿中肾α、β和多巴胺能受体的表征， 新生儿和成年羊 II）本建议的第二个主要目标 是确定循环中的儿茶酚胺和交感神经的作用， 胎儿肾对低氧血症的反应。 我们 推测在控制肾功能的机制中有一个等级 胎儿低氧血症时血流动力学和功能，肾神经激活 调节急性变化和循环儿茶酚胺调节 低氧血症的长期影响。 此外，我们建议， 机制可能有不同的发展模式。 更具体地说， 我们建议在年轻人（妊娠期少于115天）和 近足月（妊娠期超过135天;足月145天）胎羊（a） 肾神经的作用，和（B）循环的贡献 儿茶酚胺在调节肾血流动力学和功能反应中的作用 至重度（pO 2约8 mmHg）和中度（pO 2约14 mmHg）低氧血症。 此外，（c）肾胰高血糖素在减弱作用中的作用 交感神经介导的肾血管收缩， 将研究中度低氧血症。 总之，了解胎儿和新生儿肾脏对 交感神经刺激a）可能具有直接的临床相关性， 肾上腺素能药物目前用于新生儿重症监护情况， 和B）对于发展新概念至关重要， 高危妊娠胎儿宫内治疗与管理 孕妇和重病早产儿。

The overall objective of this proposal is to study, during normal and pathological conditions, the role of the sympathetic system in modulating renal hemodynamics and renal function during development using chronically catheterized and conscious fetal, newborn and adult sheep. I) The first major objective of this proposal will be to test the hypothesis that the renal hemodynamic and functional responses to Alpha, Beta, and dopamine receptor stimulation differ between fetal, newborn and adult animals. More specifically, this proposal is designed to investigate the ability of renal Alpha, Beta, and dopaminergic receptors to (a) modulate renal vascular tone, and (b) glomerular filtration rate, sodium and water metabolism, and renin release during development. Intrarenal infusion of different Alpha, Beta and dopamine agonists and antagonists will be used. Moreover, (c) results from these in vivo experiments will be correlated to in vitro characterization of renal Alpha, Beta and dopaminergic receptors in fetal, newborn and adult sheep. II) The second major objective of this proposal is to determine the role of circulating catecholamines and sympathetic nervous system in the fetal renal response to hypoxemia. We are speculating that there is a hierarchy in the mechanisms controlling renal hemodynamics and function during fetal hypoxemia, renal nerve activation modulating acute changes and circulating catecholamines modulating long-term effects of hypoxemia. Moreover, we are suggesting that these mechanisms may have different developmental patterns. More specifically, we are proposing to study in young (less than 115 days gestation) and near-term (greater than 135 days gestation; term 145 days) fetal lambs (a) the role of renal nerves, and (b) the contribution of circulating catecholamines in modulating the renal hemodynamic and functional responses to severe (pO2 about 8 mmHg) and moderate (pO2 about 14 mmHg) hypoxemia. Moreover, (c) the role of renal prostaglandins in attenuating the effects of sympathetically mediated renal vasoconstriction during severe and moderate hypoxemia will be studied. In summary, understanding of the fetal and neonatal renal responsiveness to sympathetic stimulation a) may have immediate clinical relevance since adrenergic agents are presently used in neonatal intensive care situations, and b) is essential for the development of new concepts regarding intrauterine therapy and management of the fetus during high-risk pregnancies and of severely sick premature infants.