Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension

doi:10.1016/S0022-3476(05)81552-5

The Journal of Pediatrics

Volume 123, Issue 1, July 1993, Pages 109-114

https://doi.org/10.1016/S0022-3476(05)81552-5 Get rights and content

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1±4.1 pg/ml; mean±SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8±1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6±3.6 pg/ml; p<0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0±4.7 for ECMO-treated infants vs 21.2±2.0 for non-ECMO-treated infants; p<0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.

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Citation Excerpt :
Endothelin-1 (ET-1) is released by EC and induces SMC constriction and proliferation18,19 and promotes the release of the vasoconstrictor, thromboxane.20 ET-1 levels are elevated in PPHN infants.21 Thus, the altered balance of vasoactive mediators with increased levels of vasoconstrictors and decreased vasodilators contributes to the pathogenesis of PPHN.

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^†: Supported by grants HL46481, HL41012, and M01 RR0069 from the National Institutes of Health, a March of Dimes basic research grant, and the Kempe Center at Children's Hospital.

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Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension†

J Pediatr

J Pediatr

Clin Perinatol

J Pediatr

J Pediatr

J Pediatr

Chest

J Pediatr

Life Sci

Lancet

Lancet

Etiologic mechanisms in persistent pulmonary hypertension of the newborn

Endothelium-dependent vascular responses

J Clin Invest

Regulatory functions of the vascular endothelium

N Engl J Med

Characterization of a coronary vasoconstriction produced by cultured endothelial cells

Am J Physiol

Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture

J Pharmacol Exp Ther

A novel potent vasoconstrictor peptide produced by vascular endothelial cells

Nature

Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells

FEBS Lett

Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries

Circulation