NEONATAL RESPONSES TO ALTERATIONS IN PLASMA VOLUME

我们的目的是研究前列环素(PGI2)-血管紧张素II(AII) 孤立肾小球中的相互作用可能决定离心性 肾形成完成后皮质血流的重新分配 在发育中的哺乳动物肾脏中。前列腺素(PG)的变化 猪肾小球的合成、肾素释放和AII的形成 新生儿延髓旁(JM)或浅表(SC)肾皮质 成年狗的肾脏将在体外进行测量并比较结果 随着血容量(BV)和细胞外液的变化而发育 血容量(ECFV)，循环PG、AII和精氨酸加压素水平 (AVP)，与血浆肾素活性，以及与尿PGs和 副总经理。此外，血管活性物质释放的发育差异 肾小球中的物质将在体外进行研究，当浓度达到 循环血管活性物质，如PGI2、PGE2、AII、AVP和 孵育液中的儿茶酚胺与在 新生儿和成人的动脉血浆。慢性病的影响 ECFV体内对肾小球PG合成、RR和AII的影响 JM或SC肾皮质的形成将在#年体外研究。 发育成熟的肾脏。最后，PGI2的差异性效应 体内的AII将在分离的肾小球中进行评估 慢性选择性PG或AII对发育中和成人肾脏的影响 抑制研究和BV的急性变化。放射免疫分析和 高效液相色谱后的放射层析技术 或薄层层析分离将用于测量代谢物 前列腺素I_2、前列腺素E_2、前列环素α、血栓素B_2、肾素、AI和AII及AVP的变化 培养肾小球的血浆、尿液或培养液 用未标记或放射性标记的[14C]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 肾脏血流量增加。人的生理适应 早产儿到宫外生活通常会并发 药物治疗方式，如利尿剂、升压药 药物和消炎痛，以及改变肾功能的疾病 以及PG-AII代谢。这个项目的长期目标是 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 肾小球和肾小管损害的病理生理后果 这会增加高危婴儿的发病率。

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.