The relationships between urinary prostaglandins (PGs)E2 and F2 alpha and the postnatal development of blood pressure and renal concentrating capacity were investigated in 14 pre-term and 32 full term healthy infants. Mean PGE2 and PGF2 alpha excretion was 18.9 and 10.1 ng/h/1.73 m2, respectively, in pre-term infant. In full term infants mean urinary PGE2 was significantly lower (13.4 ng/h/1.73 m2) and PGF2 alpha significantly higher (22.2 ng/h/1.73 m2). The decrease of the PGE2/PGF2 alpha ratio (P less than 0.001) was accompanied by an increase in blood pressure. High PGE2 levels in pre-term infants were inversely correlated with urinary cAMP excretion. A decreasing PGE2/PGF2 alpha ratio in full term infants was associated with increasing urinary osmolality. After intranasal administration of antidiuretic hormone (DDAVP) in 8 full term infants the increase in urinary osmolality and cAMP excretion was accompanied by a drop in PGE2 excretion to less than half the basal values. These findings suggests that the postnatal changes in urinary PG excretion are associated with a concomittant increase in blood pressure and in the concentrating capacity of the neonatal kidney.

The metabolites of prostacyclin and thromboxane A₂, 6-ketoprostaglandin F_1α and thromboxane B₂, were measured in urine of 27 preterm and 21 full-term infants. Their values were analyzed in correlation to plasma renin activity, urinary function, and systolic blood pressure. The 6-ketoprostaglandin F_1α excretion was significantly higher in the preterm infants as compared to the full-term infants (p < 0.001). This decrease of 6-ketoprostaglandin F_1α in the full-term infants was associated with a decrease in the plasma renin activity and an increase in systolic blood pressure. In contrast, the urinary excretion of thromboxane B₂ was low, without significant difference between the two groups, and there was no correlation to the parameters mentioned above.

In babies ranging in age from 1 to 25 weeks and in children between 1 and 14 years, plasma renin activity and urinary aldosterone activity were determined in relation to urinary sodium excretion. A reciprocal correlation was found demonstrating that the hyperactivity of the renin-angiotensin-aldosterone system is stimulated in infants by a low sodium intake. A second stimulus was observed in the influence of the hypothalamo-neurohypophyseal system, when the plasma renin activity was suppressed by administration of antidiuretic hormone and sodium excretion increased due to a decreased aldosterone activity. Our study suggests that there exists a feedback between the renin-angiotensin-aldosterone system and ADH release and that this feedback plays an important role in the regulation of water and electrolyte balance in the young infant.

SummaryIn 24 conscious newborn piglets the effects of 20 &kg body weight IV 1-deamino-&~-arginine-vasopressin (DDAVP) in group 1, 5 mg/kg P O indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate. urinary osmolality, creatinine clearance, total urinary and nephrogenols cyclic-adknosine 3':s'-monophosphate (CAMP) excretion. medullary cAMP content. and renal prostaglandin (PG)E2 and PGF2,, excreiion. DDAVP alone had no-signifilcant effects on the above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly Recent in vivo studies provided evidence that the restricted urinary concentrating capacity of the neonatal kidney results from the inability of the medullary cyclic adenosine 3':5'-monophosphate (CAMP) system to accumulate cAMP sufficiently in the presence of antidiuretic hormone (ADH) (14) in addition to the reduced glomerular filtration rate (2). the structural immaturity of the loop of Henle (5), and the low excretion rate of urea (7). Some observations indicate that the unresponsiveness of the cAMP system to ADH may result not only from a functional immaturity of the medullary adenylate cyclase (20,22), but additionally from the interference of renal prostaglandins (PGs) of the E-series with the hydro-osmotic action of ADH. This view is based on the following observations: (1) in isolated collecting ducts, the effect of ADH on the water permeability was blunted when PGEl was applied (10); (2) conversely, in adult mammals when PG synthesis was inhibited the effect of ADH on water reabsorption was increased (1, 3. 8. 17).High concentrations of PGs were found in urine of fetal lambs (23). and high PGEl levels were inversely correlated with urinary cAMP excretion in premature infants (15). If a relatively high PGE? formation in the kidney of neonates is indeed a restrictive parameter for renal medullary cAMP accumulation, it should be possible to increase the effect of ADH on urinary concentration by inhibiting PG synthesis.Therefore. we measured urinary concentration in newborn piglets, both before and after the administration of either DDAVP or indomethacin alone and after administration of DDAVP plus indomethacin. The studies were performed in conscious animals because it has been shown that in the unanaesthetized animal indomethacin does not change renal blood flow (24), whereas administration of this drug in the anaesthetized dog is associated with a marked fall in renal blood flow (16). MATERIALS A N D METHODS EXPERIMENTALStudies were carried out on 24 male conscious piglets (strain. Deutsche Landrasse) within the first 24 hr after birth. The animals weighed between 1000 and 1700 g and had free access to suck. The following protocol was used.Control Period. In all animals used. first all urine in the bladder was removed by puncturing the bladder suprapubically. Then the urethra was closed by glue and plaster, and each ...