ATRIAL NATRIURETIC PEPTIDE IN RENAL GROWTH

在正常肾脏生长期间，肾血流量（RBF）和 肾小球滤过率（GFR）上升，而尿效率 钠排泄（UNaV）和急性容量后的利尿 扩张也在增加。 RBF、GFR和 UNaV在代偿性肾脏生长方面相似， 肾脏质量下降。 虽然这些机制的基础 变化仍然未知，最近发现的激素，心房 利钠肽（ANP）可能起主要作用。 该肽 已显示可增加RBF、GFR、UNaV和尿流速。 此外，还发现心房ANP含量增加， 在发展过程中逐步。 拟议研究的目的是审查该条例 ANP基因转录、储存、循环水平的变化， 肾脏对ANP的生理和生化反应 老鼠的成长 确定可能影响 ANP的个体发生，通过减少 窝仔数，而肾脏生长将增强 单肾切除术 ANP mRNA水平和分布的变化 将通过北方和斑点印迹分析进行评估， 杂交技术，使用特定的cDNA探针。 心房 用放射免疫法测定心钠素的含量和分布 心房提取物和免疫细胞化学。 应对 合成大鼠ANP输注和急性容量扩张将是 通过测定血浆ANP、血浆和尿液 环GMP，其由循环ANP刺激。 效果 ANP对肾小球环GMP产生的影响 还将测量生长中的大鼠。 肾小球ANP的变化 作为肾生长的结果的受体亲和力密度将是 通过分离肾小球和肾小管进行平衡评估 约束力研究 急性肾功能衰竭的肾功能反应 扩展以及ANP输注将由 测量RBF、GFR和UNaV。 的生理作用 内源性ANP释放将在另外的动物中评估， 心房阑尾切除术 由于RBF的自动调节被改变， 肾生长，ANP输注对RBF的影响将是 在正常和降低的肾灌注压下测定。 还将研究ANP与血管紧张素II的相互作用 同时改变肾脏灌注压。 通过增加我们 了解正常人心钠素的生理调节 和适应性肾脏和躯体生长，这些研究应该 有益于患有各种肾脏疾病的婴儿和儿童， 以及肾移植捐赠者和接受者。

During normal renal growth, renal blood flow (RBF) and glomerular filtration rate (GFR) rise, while the efficiency of urine sodium excretion (UNaV) and diuresis following acute volume expansion also increase. Physiologic adaptation in RBF, GFR, and UNaV are similar in compensatory renal growth resulting from a decrease in renal mass. Although mechanisms underlying these changes remain unknown, a recently discovered hormone, atrial natriuretic peptide (ANP), may play a major role. This peptide has been shown to increase RBF, GFR, UNaV, and urine flow rate. Furthermore, atrial ANP content has been found to increase progressively during development. The purpose of the proposed studies is to examine the regulation of ANP gene transcription, storage, circulating levels, and the physiologic and biochemical renal response to ANP during renal growth in the rat. To determine factors which may influence the ontogeny of ANP, somatic growth will be accelerated by reducing litter size, while renal growth will be enhanced by uninephrectomy. Changes in ANP mRNA levels and distribution will be assessed by Northern and dot blot analysis, and in situ hybridization techniques, using a specific cDNA probe. Atrial ANP content and distribution will be studied by radioimmunoassay of atrial extracts and by immunocytochemistry. The response to synthetic rat ANP infusion and to acute volume expansion will be determined by assay of plasma ANP, and plasma and urinary cyclic GMP, which are stimulated by circulating ANP. The effect of ANP on cyclic GMP production by glomeruli isolated from growing rats will also be measured. A change in glomerular ANP receptor density of affinity as a result of renal growth will be assessed by isolation of glomeruli and tubules for equilibrium binding studies. The functional renal response to acute volume expansion as well as to ANP infusion will be studied by measurement of RBF, GFR and UNaV. The physiologic role of endogenous ANP release will be assessed in additional animals by atrial appendectomy. Since autoregulation of RBF is altered by renal growth, the effects of ANP infusion on RBF will be determined at normal and reduced renal perfusion pressure. Interaction of ANP with angiotension II will also be investigated while varying renal perfusion pressure. By increasing our understanding of the physiologic regulation of ANP during normal and adaptive renal and somatic growth, these studies should benefit infants and children with a variety of renal disorders, as well as renal transplant donors and recipients.