Chevalier R L
Department of Pediatrics, Children's Medical Center, University of Virginia, Charlottesville 22908.
Pediatr Nephrol. 1993 Oct;7(5):652-6. doi: 10.1007/BF00852574.
Although discovered little more than a decade ago, atrial natriuretic peptide (ANP) has been shown to play a significant role in the maintenance of sodium homeostasis. Immediately after birth, plasma ANP concentration is very high concurrent with right atrial dilatation and a high urinary excretion of cyclic GMP (cGMP), the second messenger for ANP. Following postnatal diuresis and natriuresis, atrial volume, plasma ANP concentration, and urinary cGMP excretion decrease to baseline levels. In the ensuing suckling period, the diuretic and natriuretic response to acute saline volume expansion are attenuated, an effect which is offset by the lower hematocrit at this age. Increase in hematocrit by isovolemic exchange transfusion results in a greater rise of plasma ANP concentration following volume expansion, but a reduced excretion of cGMP. Intravenous infusion of ANP results in greater plasma ANP concentration, and greater urinary excretion of cGMP and sodium, in adult than in young rats. This increased metabolic clearance of ANP during early development is due at least in part to increased activity of clearance receptors. In addition, neutral endopeptidase contributes to removal of circulating ANP in maturing as well as adult rats. Infusion of ANP in neonatal or adult rats results in accumulation of cGMP in glomerular podocytes, with a higher threshold for activation in immature animals. Despite the similar response of intracellular generation of cGMP following exposure to ANP in neonatal and adult rats, egression of ANP out of glomeruli is low in neonates, an effect that is due to immaturity of an organic acid transporter.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管心房利钠肽(ANP)在十多年前才被发现,但已证明它在维持钠稳态中起重要作用。出生后即刻,血浆ANP浓度非常高,同时伴有右心房扩张和作为ANP第二信使的环磷酸鸟苷(cGMP)尿排泄量增加。出生后利尿和利钠作用出现后,心房容积、血浆ANP浓度和尿cGMP排泄量降至基线水平。在随后的哺乳期中,对急性生理盐水扩容的利尿和利钠反应减弱,这一效应被该年龄段较低的血细胞比容所抵消。通过等容交换输血使血细胞比容增加,导致扩容后血浆ANP浓度升高幅度更大,但cGMP排泄减少。静脉输注ANP后,成年大鼠比幼年大鼠的血浆ANP浓度更高,cGMP和钠的尿排泄量也更大。早期发育过程中ANP代谢清除率的增加至少部分归因于清除受体活性的增加。此外,中性内肽酶在成熟大鼠和成年大鼠中均有助于清除循环中的ANP。向新生大鼠或成年大鼠输注ANP会导致肾小球足细胞中cGMP积累,未成熟动物的激活阈值更高。尽管新生大鼠和成年大鼠在接触ANP后细胞内cGMP生成的反应相似,但新生大鼠中ANP从肾小球的流出量较低,这是由于有机酸转运体不成熟所致。(摘要截取自250字)