Circulating Immunoreactive Endothelin-1 in Children with Pulmonary Hypertension: Association with Acute Hypoxic Pulmonary Vasoreactivity

Abstract

To determine whether circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, are elevated in children with pulmonary hypertension and related to the degree of hypoxic pulmonary vasoconstriction, we measured arterial and mixed venous plasma concentrations of immunoreactive ET-1 (irET-1) in 13 children during cardiac catheterization. Clinical diagnoses in seven children with pulmonary hypertension (PH) included chronic lung disease (four children), congenital heart disease after surgical repair (two children), and primary ("reactive") pulmonary hypertension (one child). Blood samples were simultaneously obtained from pulmonary artery (venous) and systemic arterial sites during baseline conditions. Plasma irET-1 was elevated in children with PH (12.3 +/- 3.4 versus 3.6 +/- 0.7 pg/ml, PH versus non-PH; p < 0.01). Arterial/venous irET-1 ratios in the PH group (1.1 +/- 0.2) were not different from those in the non-PH group. During acute hypoxia, mean Ppa increased from 27 +/- 3 to 40 +/- 5 mm Hg. Basal irET-1 correlated strongly with the degree of elevation of mean Ppa during acute hypoxia (r = 0.69; p < 0.02). We conclude that irET-1 levels are often elevated in children with PH, and they are strongly correlated with pulmonary vasoreactivity during acute hypoxia. Whether elevated irET-1 levels contribute directly to or are markers of altered pulmonary vascular tone and reactivity in children with PH remains speculative.

Recent Advances in Endothelin Research on Cardiovascular and Endocrine Systems.

“…A similar close relationship between the plasma ET-1 levels and pulmonary vascular resistance was found in patients with pulmonary hypertension [81][82][83][84][85], suggesting a role of ET-1 in humans also. In addition, ET-1 is synthesized and released from respiratory epithelial cells, suggesting a potential pathological role in bronchial asthma (for review see [11,12]).…”

Endothelin receptor expression in idiopathic pulmonary arterial hypertension: effect of bosentan and epoprostenol treatment

“…Treatment with prostacyclin, endothelin receptor antagonists and phosphodiesterase inhibitors aims to promote dilatation and reparative remodelling of the pulmonary arteries, and has improved survival and quality of life but is not curative [1]. The only therapeutic option for endstage disease is lung transplantation.The endothelin ET-1 is a potent vasoconstrictor and smooth muscle cell mitogen [2] that is important in the pathobiology of pulmonary arterial hypertension [3]. In humans with IPAH, plasma endothelin levels are elevated [4], endothelin-converting enzyme activity is enhanced [5] and lung expression of endothelin is increased [6].…”

“…The endothelin ET-1 is a potent vasoconstrictor and smooth muscle cell mitogen [2] that is important in the pathobiology of pulmonary arterial hypertension [3]. In humans with IPAH, plasma endothelin levels are elevated [4], endothelin-converting enzyme activity is enhanced [5] and lung expression of endothelin is increased [6].…”

Long-term efficacy of bosentan in treatment of pulmonary arterial hypertension in children

“…After 3 yrs, bosentan was continued as monotherapy in only 21% of children with IPAH, but in 69% of repaired cases and 56% of those with Eisenmenger syndrome. The Kaplan-Meier survival estimates for the 101 patients were 96, 89, 83 and 60% at 1, 2, 3 and 5 yrs, respectively.A treatment regime that includes bosentan is safe and appears to be effective in slowing disease progression in children with PAH.KEYWORDS: Bosentan, idiopathic pulmonary arterial hypertension, paediatric pulmonary arterial hypertension, pulmonary hypertension in congenital heart disease E ndothelin-1 (ET) is important in the pathobiology of pulmonary arterial hypertension (PAH) [1][2][3] and plasma levels are elevated in both adults and children with PAH. …”