Reduced Pulmonary Removal of Circulating Endothelin-1: A New Marker of Human Pulmonary Hypertension

Abstract

The pulmonary vascular endothelium is an important site for both clearance and production of endothelin-1 (ET-1). Pulmonary hypertension (PH) is associated with increased circulating ET-1 levels that may contribute to the disease process: it is presently unknown if a reduced clearance, and increased production or a combination of both are responsible. We studied the pulmonary metabolism of ET-1 in 13 controls (C), and 17 patients with PH (12 mitral stenoses, 4 CHF, I idiopatic) by combining the indicator dilution technique with measurements of immunoreactive ET-1 levels (IRET-1). We measured percent I¹²⁵-ET-1 extraction (Ext) as well as net ET-1 production and survival (amount of ET-1 surviving passage through the lungs). The permeability-surface area product (PS) for ET-1 removal was computed using the Renkin model. In controls, aortic IRET-1 levels (0.67 ± 0.10 pg/ml, mean ± SE) were not different from pulmonary artery (0.61 ± 0.08 pg/ml). Levels were higher in PH (p<0.05) with a tendency for higher aortic (1.23 ± 0.16 pg/ml) than pulmonary artery levels (1.07 ± 0.19 pg/ml, p=0.07).