REGULATION OF RENAL RESPONSE TO ANP IN EARLY DEVELOPMENT

在出生后的哺乳期，肾有利钠剂和利尿剂

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.