REGULATION OF RENAL RESPONSE TO ANP IN EARLY DEVELOPMENT

在出生后哺乳期，肾利钠和利尿剂 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目前的限制。 母乳和钠的保存对于正常的躯体是必要的 成长。在这个项目中要检验的假设是，心房 利钠肽(ANP)对早期钠稳态的调节作用 后天发育。与成人相比，增强的钠守恒 在哺乳期可能是由于心钠素分泌受到抑制 或降低肾脏对循环ANP的反应。至 确定钠摄入对这些机制的影响，饮食中的钠 将通过人工饲养程序在断奶前的大鼠中得到控制 (正常和高钠摄入量)。这些回答将与那些 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(Northern分析)和 心肌ANP免疫反应阳性。对ANP的肾脏反应将是 由环状GMP(CGMP)的肾内定位决定 用于ANP的信使)使用免疫组织化学，并通过测量 肾小球滤过率、肾小球体积和cGMP生成 分离的肾小球暴露于ANP。因为cGMP的运输出了 肾小球细胞可能介导对ANP的反应，其机制是 CGMP在新生儿和成人肾小球中的表达 ANP.鉴于肾素-血管紧张素系统的活性增强 (RAS)在早期发育中，受肾脏血管紧张素II的调节 对ANP的反应也将在完整的大鼠和分离的大鼠中进行研究 肾小球。此外，ANP对RAS的对抗以及ANP的作用 单侧输尿管新生大鼠肾神经的研究 梗阻(进一步激活成熟早期的RAS)。通过 慢性心绞痛患者ANP的形成及其对肾脏反应的研究 在出生后早期发育中控制钠摄入量的结果 这些研究将导致对生理的更好的理解 心钠素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.