Relation between endothelin-1 spillover in the lungs and pulmonary vascular resistance in patients with chronic heart failure

Abstract

Objectives. The aim of this study was to clarify the origin of plasma endothelin-1 and to determine the relation between pulmonary vascular resistance and endothelin-1 secretion in the pulmonary circulation in patients with chronic congestive heart failure.Background. Plasma levels of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, are increased in congestive heart failure, but the source has not been clarified. Recent studies have indicated a relation between endothelin-1 and pulmonary hypertension. We therefore evaluated the contribution of endothelin-1 secretion in the pulmonary circulation to the regulation of pulmonary vascular resistance in patients with chronic heart failure.Methods. A comparison was made of the plasma levels of endothelin-1 between the main pulmonary artery and the pulmonary capillary wedge region, as well as between the femoral artery and the femoral vein in 62 patients with chronic heart failure. Stepwise multivariate regression analysis was used to detect independent predictors of pulmonary vascular resistance among the various vasoconstrictor hormones in these patients.Results. There was no significant difference in plasma endothelin-1 levels between the femoral artery and vein. In contrast, plasma endothelin-1 increased significantly from the main pulmonary artery to the pulmonary capillary wedge region ([mean ± SEM] 3.1 ± 0.23 vs. 4.6 ± 0.36 pg/ml, p < 0.01), and the increase was related to the severity of heart failure. Among the various vasoconstrictor factors, such as plasma active renin concentration, plasma angiotensin II, plasma norepinephrine, femoral venous plasma endothelin-1 and pulmonary endothelin-1 spillover, only endothelin-1 spillover in the lungs showed an independent and significant correlation with pulmonary vascular resistance (r = 0.82, p < 0.001).Conclusions. The main source of circulating endothelin-1 is not the peripheral vascular bed but the pulmonary vascular bed in patients with chronic heart failure. In addition, endothelin-1 secretion in the lungs may regulate the pulmonary vascular resistance in patients with chronic heart failure. These findings are consistent with a significant role for endogenous endothelin-1 in the pathophysiology of heart failure, espscially in the pulmonary circulation.