SYMPATHETIC CONTROL OF RENAL FUNCTION DURING DEVELOPMENT

本建议书旨在确定 儿茶酚胺与交感神经系统对肾脏的调节 有意识和慢性发育过程中的血流动力学和功能 留置尿管的胎羊、新生羊和成年羊。此外，这些生理上的 这些发现将与体外测定α、β和 发育中肾脏中的多巴胺能受体。具体目标是 研究：1)肾脏α、β和多巴胺能受体 在发育过程中调节肾脏血管张力；以及2) α、β和多巴胺能受体调节肾小球滤过 在发育过程中，钠和水的代谢以及肾素的分泌。 肾内α、β和多巴胺能激动剂和拮抗剂 管理。肾脏血流量的变化将通过脉冲式 多普勒血流探头。 这些实验将揭示关于 肾血管和肾功能反应的调节机制 胎儿、新生儿和成人发育过程中的交感神经刺激 羊。此外，这些研究将首次允许相互关联 肾交感神经系统的生理特征 大鼠肾脏肾上腺素能受体(α、β和DA)的体外特性 从胎儿发育到成年的同一种动物。这个 从这些实验中获得的信息将具有重要的临床意义 α和β肾上腺素能受体激动剂和拮抗剂的意义 和多巴胺一样，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是 目前已知在早产儿中。 候选人中村博士已经完成了他的临床培训 新生儿学，并在过去两年(1983年1月至12月)一直得到支持 1984年)被国家研究服务奖(F32-HD-06438)授予实验室 发展生理学领域的研究。他的研究训练 以及他在那段时间的研究成果 是候选人认真打算进入一项成功的 学术研究生涯。 发起人罗比拉德博士是一位顶尖的发育生理学家， 胎儿肾功能方面的专业知识。他的研究技巧和 使用非麻醉和慢性胎羊模型的调查技巧 将为应聘者提供必要的独特技能 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.