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


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 125I-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<0.001). Mixed venous (MV) and aortic ET-1 levels doubled with HF. There was a plasma ET-1 gradient across the lungs of sham rats (MV-aortic levels, 0.21+/-0.12 pg/mL) but not in lungs of HF rats (0.01+/-0.17 pg/mL). Plasma ET-1 levels correlated closely and inversely with ET-1 extraction (P<0.001).


CONCLUSIONS
HF is associated with reduced pulmonary ET-1 clearance that contributes to the increase in circulating levels.
Dupuis
J
J
Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada. dupuis@icm.umontreal.ca
Rouleau
J L
JL
Cernacek
P
P
D000818:Animals; D002303:Cardiac Output, Low / Q000097:blood* / Q000209:etiology; D019332:Endothelin-1 / Q000097:blood / Q000493:pharmacokinetics*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1