REGULATION OF RENAL RESPONSE TO ANP IN EARLY DEVELOPMENT

在出生后哺乳期， 与成人相比，对急性容量扩张的反应减弱。 此外，新生儿的钠摄入量受到以下因素的限制： 母乳和钠的保存是必要的正常的躯体 增长 在本项目中要检验的假设是， 利钠肽（ANP）介导或调节早期钠稳态 产后发育 与成年人相比， 在哺乳期可能是由于抑制ANP的生产， 或降低肾对循环ANP的反应。 到 确定钠摄入量对这些机制的影响，膳食钠 将通过人工饲养程序在断奶前大鼠中进行控制 （正常和高钠摄入量）。 这些回答将与 控制钠摄入量的成年大鼠。 ANP的生产将是 通过测量ANP基因表达（北方分析）进行研究， 免疫反应性心钠素。 肾脏对ANP的反应将是 通过肾内定位的环GMP（cGMP，第二 ANP信使），并通过测量 肾小球滤过率、肾小球体积和cGMP生成 离体肾小球暴露于ANP。 因为cGMP的运输 肾小球细胞可能介导了对ANP的反应，这是 在暴露于以下物质的新生儿和成人肾小球中， ANP。 鉴于肾素-血管紧张素系统的活性增强， (RAS)在早期发育中，肾血管紧张素II的调节 对ANP的反应也将在完整大鼠和分离的大鼠中进行研究。 肾小球 此外，ANP对RAS的抵消作用以及 将在单侧输尿管狭窄的新生大鼠中研究肾神经 阻塞（在早期成熟中进一步激活RAS）。 通过 研究ANP的形成和肾脏对ANP的反应， 控制出生后早期发育中的钠摄入量， 这些研究将有助于人们更好地理解 ANP的作用，以及改善危重新生儿的管理 婴儿。

In the postnatal suckling period, the renal natriuretic and diuretic response to acute volume expansion is attenuated compared to the adult. Moreover, sodium intake in the neonate is limited by that present in maternal milk, and sodium conservation is necessary for normal somatic growth. The hypothesis to be tested in this project is that atrial natriuretic peptide (ANP) mediates or modulates sodium homeostasis in early postnatal development. Compared to the adult, enhanced sodium conservation in the suckling period could result from either suppressed ANP production by the myocardium, or reduced renal response to circulating ANP. To determine the effects of sodium intake on these mechanisms, dietary sodium will be controlled in preweaned rats by an artificial rearing procedure (normal and high sodium intake). The responses will be compared to those of adult rats on controlled sodium intake. Production of ANP will be investigated by measuring ANP gene expression (Northern analysis) and immunoreactive ANP in the myocardium. The renal response to ANP will be determined by intrarenal localization of cyclic GMP (cGMP, the second messenger for ANP) using immunohistochemistry, and by measurement of glomerular filtration rate, glomerular volume, and cGMP generation by isolated glomeruli exposed to ANP. Because transport of cGMP out of the glomerular cells may mediate the response to ANP, the mechanism of egression of cGMP will be sought in neonatal and adult glomeruli exposed to ANP. In view of the enhanced activity of the renin-angiotensin system (RAS) in early development, modulation by angiotensin II of the renal response to ANP will also be investigated in intact rats and isolated glomeruli. In addition, counteraction of the RAS by ANP and the role of the renal nerves will be studied in neonatal rats with unilateral ureteral obstruction (which further activates the RAS in early maturation). By investigating the formation of ANP and the renal response to ANP during controlled sodium intake in early postnatal development, the results of these studies will lead to an improved understanding of the physiologic role of ANP, as well as to improved management of critically ill neonatal infants.