REGULATION OF ANP SYNTHESIS AND RESPONSE 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动脉 利钠肽(ANP)介导或调节心肌细胞内钠稳态 出生后早期发育。与成人相比，增强的钠 哺乳期的保护可能是由于抑制了 由心肌产生心钠素，或降低肾脏对 循环心钠素。为了确定钠摄入量对这些指标的影响 机制，饮食钠将被控制在一个预先断奶的大鼠 人工饲养程序(正常和高钠摄入量)。这个 这些反应将与成年大鼠对受控钠的反应进行比较。 入口处。ANP的生产将通过测量ANP在 心肌。肾(Northern分析)和免疫反应性心钠素 心肌。肾脏对心钠素的反应将由肾内决定。 心钠素第二信使cGMP的定位研究 免疫组织化学，通过测量肾小球滤过率， 肾小球体积和肾小球cGMP的产生 ANP.因为cGMP在肾小球细胞外的转运可能在 对ANP的反应，cGMP的释放机制将在 新生儿和成人肾小球暴露于ANP。鉴于增强的 肾素-血管紧张素系统(RAS)在早期发育中的活性， 血管紧张素II对肾脏对心钠素的反应也将是 在完整的大鼠和分离的肾小球中进行了研究。此外, 心钠素对新生大鼠血管紧张素转换酶的拮抗作用 单侧输尿管梗阻(这在早期进一步激活RAS 成熟)。通过研究ANP的形成和肾脏 出生后早期控制钠摄入量对心钠素的反应 发展，这些研究的结果将导致改善 对心钠素生理作用的理解以及改进 危重新生儿的处理。

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 arterial 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 in the myocardium. The renal (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 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.