Reduced pulmonary clearance of endothelin-1 contributes to the increase of circulating levels in heart failure secondary to myocardial infarction.

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Abstract
Background —The pulmonary vascular bed is a major site for endothelin-1 (ET-1) clearance. A reduced clearance could contribute to the increase in circulating ET-1 levels found in heart failure (HF). We therefore evaluated the effect of HF on pulmonary ET-1 clearance and on plasma ET-1 concentrations. Methods and Results —Rats with myocardial infarction (n=24) were compared with sham-operated rats (n=22). The lungs were isolated and perfused at a constant flow rate of 10 mL/min. Pulmonary ET-1 clearance was measured by the single-bolus indicator-dilution technique with 125 I-labeled ET-1. Infarct rats developed HF with mild pulmonary hypertension. ET-1 extraction was reduced by HF from 63±1.5% to 41±4.5% (mean±SEM, P P Conclusions —HF is associated with reduced pulmonary ET-1 clearance that contributes to the increase in circulating levels.