SYMPATHETIC CONTROL OF RENAL FUNCTION DURING DEVELOPMENT

本提案旨在确定以下机构的职能作用： 儿茶酚胺和交感神经系统在调节肾功能中的作用 有意识和慢性发育过程中血流动力学和功能 插入导管的胎羊、新生羊和成年羊。 此外，这些生理 这些发现将与体外测定α、β和 发育中的肾脏中的多巴胺能受体。 具体的目标是 研究：1）肾α，β和多巴胺能受体的能力， 在发育过程中调节肾血管张力;和2） 调节肾小球滤过的α、β和多巴胺能受体 发育过程中钠、水代谢和肾素分泌的变化。 肾内α、β和多巴胺能激动剂和拮抗剂将被 管理。 肾血流量的变化将通过脉冲血流仪测定。 多普勒血流探头 这些实验将揭示有关 调节肾血管和肾功能反应的机制 胎儿、新生儿和成人发育期间的交感神经刺激 羊 此外，这些研究将首次允许相关性 肾交感神经系统的生理特征， 肾肾上腺素受体（α、β和DA）的体外表征 同一动物从胎儿到成年的发育过程。 的 从这些实验中获得的信息将具有显著的临床意义。 由于α和β肾上腺素受体激动剂和拮抗剂， 以及多巴胺目前用于新生儿重症监护情况。 然而，肾血管系统对这些药物的敏感性并不 目前已知的早产儿。 博士候选人中村已完成临床培训， 在过去的两年里（1983年1月至12月）， 1984年）获国家研究服务奖（F32-HD-06438）做实验室 发育生理学领域的研究。 他的研究训练 背景以及他在那段时间的研究成果 是候选人的严重意图进入一个成功的证据 学术研究生涯。 博士赞助商Robillard是一位最重要的发育生理学家， 胎儿肾功能方面的专业知识 他的研究技术和 使用未麻醉和慢性胎羊模型的研究技巧 将为候选人提供所需的独特技能， 独立研究。

This proposal is designed to determine the functional roles of catecholamines and the sympathetic nervous system in modulating renal hemodynamics and function during development in conscious and chronically catheterized fetal, newborn and adult sheep. Moreover, these physiological findings will be correlated to in vitro determination of alpha, beta and dopaminergic receptors in the developing kidney. Specific aims are to study: 1) the ability of renal alpha, beta and dopaminergic receptors to modulate renal vascular tone during development; and 2) the ability of alpha, beta and dopaminergic receptors to modulate glomerular filtration rate, sodium and water metabolism and renin secretion during development. Intrarenal alpha, beta and dopaminergic agonists and antagonists will be administered. Changes in renal blood flow will be determined by a pulsed doppler flow probe. These experiments will reveal important information concerning the mechanisms modulating the renal vascular and renal functional response to sympathetic stimulation during development in fetal, newborn and adult sheep. Moreover, for the first time these studies will permit correlation of the physiologic characteristics of the renal sympathetic system with the in vitro characterization of renal adrenoceptors (alpha, beta and DA) in the same animal during development from fetal to adult life. The information obtained from these experiments will have significant clinical implications since alpha and beta adrenoceptor agonists and antagonists, as well as dopamine, are presently used in neonatal intensive care situations. The sensitivity of the renal vasculature to these agents, however, is not currently known in premature infants. Dr. Nakamura, the candidate, has completed his clinical training in neonatology, and has been supported for the past two years (Jan 1983 to Dec 1984) by a National Research Service Award (F32-HD-06438) to do laboratory research in the field of developmental physiology. His research training background as well as his research productivity during that period of time are evidence of the candidate's serious intent to enter into a successful academic research career. Dr. Robillard, the sponsor, is a foremost developmental physiologist with specific expertise in fetal renal function. His research techniques and investigative skills using the unanesthetized and chronic fetal lamb model will provide the candidate with unique skills necessary to pursue independent research.