Urinary Excretion of Endogenous Ouabain-Like Substance Is Reduced in NaCl Supplemented Premature Infants

Abstract

Ouabain or an isomer has been identified as endogenous ouabain-like substance (EOLS). The role of EOLS in the adaptation of premature infants to alterations of sodium balance was investigated by measuring urinary ouabain excretion serially in 9 low birth weight premature infants with (group S, mean birth weight 1,578 g, mean gestational age 30.4 weeks) and without (group NS, mean birth weight 1,537 g, mean gestational age 30.8 weeks) NaCl supplementation. The study was performed on the 7th day and weekly thereafter until the 5th week of life. NaCl supplementation was given in a dose of 3–5 and 1.5–2.5 mmol/kg/day at the postnatal ages of 8–21 and 22–35 days, respectively. Prior to NaCl supplementation, urinary ouabain excretion was similar in the two groups (146.2 ± 16.8 pg/kg/h in group S versus 180.0 ± 9.6 pg/kg/h in group NS) and remained at about the same level throughout the study when supplemental NaCl was provided. In infants of group NS, urinary ouabain excretion increased significantly by the 3rd week (p < 0.01) and no consistent change occurred later on. As a result, the differences in urinary ouabain excretion between the two groups proved to be significant during weeks 2–5 (p < 0.001). Essentially the same pattern of ouabain excretion was seen when it was expressed in terms of pg/mg creatinine. In infants receiving high sodium diet there was a significant positive correlation between urinary sodium and ouabain excretion. It is concluded that premature infants receiving low sodium intake have elevated EOLS excretion by the 3rd week of life. Although the relationship between ouabain and sodium excretion in supplemented premature infants suggests some physiological significance for sodium excretion, ouabain does not appear to be regulated by extracellular volume.

Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats

“…Thus it appears that in F344 ϫ NB rats, MBG is more responsive to a high NaCl intake, whereas OLC is more responsive to the isolation stress. Although in some previous reports OLC was shown to be responsive to high NaCl intake in normotensive rats (7,49), the results of other studies indicate that OLC is not stimulated by high NaCl or that it is responsive to high NaCl intake in animals that exhibit the salt-sensitive blood pressure increases (5,46,48). Thus Yamada and co-workers (48), using a highly specific ouabain antibody, demonstrated that although Wistar rats did not exhibit increases in plasma OLC levels during high NaCl intake, such increases did occur in NaCl-loaded Wistar rats after renal mass reduction.…”

The Na+/Ca2+ exchanger: A possible link between oxidative stress and endogenous ouabain in hypertension

“…Ouabain like substance is also found in infants [132]. In the urine of premature infants supplemented with NaCl and in infants treated with furosemide, the level of ouabain excreted in the urine is reduced significantly [133,134]. Ouabain and ouabain-like substances are also found in the blood of hypertensive pregnant mothers and their infants [135][136][137].…”

Pathomechanisms of Prenatally Programmed Adult Diseases

“…It is tempting to postulate, therefore, that the activated renin-angiotensin II-AT1R pathway, either directly or indirectly via the generation of superoxide, enhances the redox-sensitive ADMA accumulation [163]. It is also to be considered that the production of the vasoactive adrenal steroid ouabain is also elevated, and its elevation proved to be dependent of the activity of the RAAS [164]. As ouabain has been suggested to mediate superoxide and peroxynitrite production, it may also contribute to endothelial dysfunction, and to the development of cardiovascular diseases later in life [165,166].…”