Endothelin-1-and endothelin-receptors in lung biopsies of patients with pulmonary hypertension due to congenital heart disease

Endothelin-1 (ET-1), with its vasoconstrictive and proliferation-stimulatin g effects, could play a role in the pathogenesis of primary pulmonary hyper tension. We investigated the relationship between the ET-1 like immunoreact ivity and the ET-receptor density, the grade of the pulmonary vasculopathy, and properties of the pulmonary circulation in patients with pulmonary hyp ertension due to congenital heart disease. Twenty-six patients with a median age of 1 year and 1 month (6 weeks - 17 y ears - 9 months) were assigned to group I (n = 15) with a pulmonary to syst emic flow ratio (Qp/Qs) greater than or equal to 1.5 and a pulmonary to sys temic resistance ratio (Rp/Rs) less than or equal to 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 ETB-receptor density in lung arteries (p < 0.05) and parenchyma (p < 0.01) than patients in group I. Pa tients with the highest ET-1 like immunoreactivity in lung artery walls als o showed a trend towards a higher ETA-receptor density. The ETB-receptor ex pression 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 co ngenital heart disease.