Endothelin-1- and Endothelin-Receptors in Lung Biopsies of Patients with Pulmonary Hypertension due to Congenital Heart Disease

Abstract

Endothelin-1 (ET-1), with its vasoconstrictive and proliferation-stimulating effects, could play a role in the pathogenesis of primary pulmonary hypertension. We investigated the relationship between the ET-1 like immunoreactivity and the ET-receptor density, the grade of the pulmonary vasculopathy, and properties of the pulmonary circulation in patients with pulmonary hypertension due to congenital heart disease.

Twenty-six patients with a median age of 1 year and 1 month (6 weeks–17 years–9 months) were assigned to group I (n = 15) with a pulmonary to systemic flow ratio (Qp/Qs) ≥ 1.5 and a pulmonary to systemic resistance ratio (Rp/Rs) ≤ 0.3 (“high flow–low resistance group”) and to group II (n = 11) with a Qp/Qs < 1.5 and an Rp/Rs > 0.3 (“low flow–high resistance group”).

Patients belonging to group II showed a higher ET_A-receptor density in lung arteries (p < 0.05) and parenchyma (p < 0.01) than patients in group I. Patients with the highest ET-1 like immunoreactivity in lung artery walls also showed a trend towards a higher ET_A-receptor density. The ET_B-receptor expression was low and not related to any of the above factors.

Our results suggest that the paracrine lung ET-1 system is up-regulated in pediatric patients with secondary pulmonary hypertension associated with congenital heart disease.