NEONATAL RESPONSES TO ALTERATIONS IN PLASMA VOLUME

新生儿对血浆容量变化的反应

• 批准号: 3234788
• 负责人: BILLY S ARANT
• 金额: $ 12万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234788
• 关键词: angiotensin II; arginine vasopressin; blood volume; diuretics; fatty acid biosynthesis; high performance liquid chromatography; indomethacin; newborn human (0-6 weeks); plasma; prostacyclins; prostaglandin analogs; prostaglandins; radioimmunoassay; radiotracer; renal cortex; renal glomerulus; renal tubular transport; renin

Our purpose is to investigate prostacyclin(PGI2)-angiotensin II (AII) interactions in isolated glomeruli which may determine the centrifugal redistribution of cortical blood flow when nephrogenesis has been completed in the developing mammalian kidney. Changes in prostaglandin (PG) synthesis, renin release (RR) and AII formation by glomeruli isolated from the juxtamedullary (JM) or superficial (SC) renal cortex of neonatal and adult dog kidneys will be measured in vitro and results compared developmentally with changes in blood volume (BV) and extracellular fluid volume (ECFV), with circulating levels of PG, AII and arginine vasopressin (AVP), with plasma renin activity, and with urinary excretion of PGs and AVP. Moreover, developmental differences in release of vasoactive substances from glomeruli will be studied in vitro when the concentrations of circulating vasoactive substances such as PGI2, PGE2, AII, AVP and catecholamines in the incubation medium are similar to those measured in arterial plasma of neonates and adults. The influence of chronic differences in ECFV in vivo on glomerular PG synthesis, RR and AII formation in the JM or SC renal cortex will be studied in vitro in developing and mature kidneys. Finally, the differential effects of PGI2 and AII in vivo will be assessed in isolated glomeruli harvested from developing and adult kidneys subjected to chronic selective PG or AII inhibition studies and to acute changes in BV. Radioimmunoassay and radiochromatography techniques after high performance liquid chromatography or thin layer chromatography separation will be used to measure metabolites of PGI2, PGE2, PGF2Alpha, thromboxane B2 renin, AI and AII and AVP in plasma, urine or incubation medium in which glomeruli have been incubated with unlabeled or radiolabeled [14C] arachidonic acid. Glomerular filtration rate during mammalian renal development increases pari passu with increments in renal blood flow. The physiologic adaptation of the premature human infant to extrauterine life is often complicated by therapeutic modalities, by pharmacologic agents such as diuretics, pressor drugs and indomethacin, and by diseases which alter both renal function as well as PG-AII metabolism. The long-term objective of this project is to identify physiologic mechanisms that effect changes in renal function during normal development, but when perturbed in the neonatal period have pathophysiologic consequences to impair renal glomerular and tubular functions and to increase morbidity among high-risk infants.

本研究旨在探讨前列环素（PGI_2）-血管紧张素II（AII） 分离肾小球中的相互作用，这可能决定离心 肾发生完成时皮质血流的重新分布 哺乳动物肾脏的发育。 前列腺素（PG）的变化 分离肾小球合成、肾素释放（RR）和AII形成 新生儿的髓质（JM）或浅表（SC）肾皮质， 将在体外测量成年犬肾脏，并比较结果 随着血容量（BV）和细胞外液的变化， 容积（ECFV），以及PG、AII和精氨酸加压素的循环水平 (AVP)与血浆肾素活性、尿前列腺素排泄量及 AVP。 此外，血管活性物质释放的发育差异 将在体外研究来自肾小球的物质， 循环血管活性物质如PGI 2、PGE 2、AII、AVP和 培养介质中的儿茶酚胺类似于 新生儿和成人的动脉血浆。 慢性病的影响 体内ECFV对肾小球PG合成、RR和AII的差异 将在体外研究JM或SC肾皮质中的形成， 发育和成熟的肾脏。 最后，PGI 2的差异效应 和AII在体内将在分离的肾小球中进行评估，所述分离的肾小球从 发育中和成年肾脏接受慢性选择性PG或AII 抑制研究和BV的急性变化。 放射免疫法和 高效液相色谱后放射性色谱技术 或薄层色谱分离将用于测量代谢物 PGI 2、PGE 2、PGF 2 α、血栓素B2、肾素、AI和AII以及AVP的变化。 血浆、尿液或培养肾小球的培养基 未标记或放射性标记的[14 C]花生四烯酸。 肾小球 哺乳动物肾脏发育过程中的滤过率增加 肾血流量增加。 的生理适应 早产人类婴儿到子宫外的生活通常是复杂的， 治疗方式，通过药物如利尿剂、加压剂 药物和吲哚美辛，以及改变肾功能， 以及PG-AII代谢。 该项目的长期目标是 确定影响肾功能变化的生理机制 在正常发育期间，但在新生儿期受到干扰时， 损害肾小球和肾小管的病理生理后果 功能，并增加高风险婴儿的发病率。