ONTOGENESIS OF THE SYMPATHETIC CONTROL OF RENAL FUNCTION

这项建议的总体目标是研究在正常和 病理状态，交感神经系统在调节中的作用 慢性应用于发育过程中的肾血流动力学和肾功能 留置尿管，清醒的胎儿、新生儿和成年绵羊。I)第一个 这项提案的主要目标将是检验以下假设： 肾血流动力学和肾功能对α、β和多巴胺的反应 受体刺激在胎儿、新生动物和成年动物之间有所不同。更多 具体地说，这项建议旨在调查肾脏的能力 α、β和多巴胺能受体(A)调节肾血管 (B)肾小球滤过率、钠和水代谢，以及 肾素在发育过程中的释放。肾内注入不同的阿尔法， 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相关联。 胎儿肾脏α、β和多巴胺能受体的特征 初生羊和成年羊。二)本提案的第二个主要目标 是为了确定循环中儿茶酚胺和交感神经的作用 神经系统在胎儿肾脏对低氧血症的反应。我们是 推测在控制肾脏的机制中有一个等级 胎儿低氧血症、肾神经兴奋时的血流动力学和功能 调节急性变化与循环儿茶酚胺的调节 低氧血症的长期影响。此外，我们建议这些 机制可能有不同的发展模式。更确切地说， 我们建议在年轻的时候(怀孕不到115天)和 近期(妊娠超过135天；足月145天)胎羔羊(A) 肾神经的作用，以及(B)循环的作用 儿茶酚胺对肾脏血流动力学和功能反应的调节作用 至重度(氧分压约8毫米汞柱)和中度(氧分压约14毫米汞柱)低氧血症。 此外，(C)肾脏前列腺素在减轻影响方面的作用 交感神经介导的肾血管收缩在严重和 将对中度低氧血症进行研究。 总之，对胎儿和新生儿肾脏反应性的理解 交感神经刺激a)可能具有直接的临床意义，因为 肾上腺素能药物目前用于新生儿重症监护情况， 和b)对以下方面的新概念的发展至关重要 高危胎儿的宫内治疗与处理 怀孕和病情严重的早产儿。

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.