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The present study was undertaken to define the possible role of endogenous ouabain-like substance (EOLS) in controlling renal excretory pattern, in mediating the renal responses to furosemide and in inducing endocrine reactions in furosemide-treated neonates. Ten newborn infants with mean birthweight of 2,752 g and mean gestational age of 37.1 weeks were given furosemide in a dose of 1 mg/kg. Prior to and following furosemide therapy, urine was collected for a period of 12 h and analyzed for creatinine, osmolality, sodium and potassium, as well as for EOLS, arginine vasopressin (AVP), aldosterone and endothelin-1 (ET-1). In response to furosemide administration, urine flow rate and urinary osmolar, sodium and potassium excretion increased significantly, whereas creatinine excretion remained unchanged. Furthermore, following furosemide therapy, urinary excretion of EOLS (148.7 ± 70.8 vs. 200.1 ± 98.1 pg/kg/h) and AVP (19.5 ± 5.4 vs. 27.8 ± 7.8 pg/kg/h) tended to increase, whereas ET-1 (36.0 ± 5.6 vs. 61.4 ± 8.7fmol/kg/h, p < 0.01) and aldosterone (507 ± 120 vs. 751 ± 203 ng/kg/h, p < 0.05) increased significantly. Prior to furosemide, urinary EOLS excretion was found to correlate positively with diuresis (r = 0.80, p < 0.01), sodium (r = 0.91, p < 0.001), creatinine (r = 0.75, p < 0.001), osmolar (r = 0.96, p < 0.001), ET-1 (r = 0.90, p < 0.001) and AVP (r = 0.92, p < 0.001) excretion. After furosemide, urinary EOLS excretion significantly correlated only with diuresis (r = 0.69, p < 0.05), ET-1 (r = 0.77, p < 0.01) and AVP (r = 0.92, p < 0.001). Urinary EOLS proved to be independent of aldosterone excretion irrespective of furosemide administration. It is concluded that urinary EOLS excretion is closely related to neonatal renal excretory pattern and it may have a role in controlling diuresis and natriuresis. The renal response to furosemide appears to be independent of EOLS, although interdependent endocrine reactions can be induced by furosemide which may modulate the production rate and urinary excretion of EOLS.

The present study was undertaken to establish the developmental pattern of urinary endothelin-1 (ET-1) excretion and to define its possible role in mediating pathophysiological changes related to perinatal asphyxia/infection and dopamine treatment. Urinary ET-1 levels were measured by radioimmunoassay in 7 full-term neonates (mean gestational age 39.3 weeks) on days 1, 3 and 5, and in 9 pre-term neonates (mean gestational age 30.8 weeks) on days 1, 3, 5, 7 and weekly thereafter for 5 consecutive weeks. The results were compared with those of three age-groups of 30 normal children (4-8 years, 9-12 years and 13-18 years); each group consisted of 10 children. The influence of severe cardiopulmonary distress (n = 16, mean gestational age 33.9 weeks, post-natal age 3.3 days) and dopamine administration in a dose of 2 micrograms/min per kg (n = 10, mean gestational and post-natal ages 32.1 weeks and 5.6 days, respectively) were also studied. In full-term infants, ET-1 concentration fell from 34.3 +/- 1.8 pmol/l on day 1 to 21.5 +/- 1.5 pmol/l on day 5 (P < 0.01). In premature infants its absolute value and its post-natal fall were similar in the 1st week and no further change occurred in weeks 2-5; it stabilized at levels between 17.1 +/- 2.2 and 16.7 +/- 1.7 pmol/l. These concentrations tended to be lower than those of 25.5 +/- 1.3, 23.0 +/- 1.0 and 26.2 +/- 0.7 pmol/l measured in three groups of older children.(ABSTRACT TRUNCATED AT 250 WORDS)