J. Dupuis et al., REDUCED PULMONARY CLEARANCE OF ENDOTHELIN-1 CONTRIBUTES TO THE INCREASE OF CIRCULATING LEVELS IN HEART-FAILURE SECONDARY TO MYOCARDIAL-INFARCTION, Circulation, 98(16), 1998, pp. 1684-1687
Citations number
24
Categorie Soggetti
Peripheal Vascular Diseas",Hematology,"Cardiac & Cardiovascular System
Background-The pulmonary vascular bed is a major site for endothelin-l
(ET-1) clearance. A reduced clearance could contribute to the increas
e 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 infarcti
on (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 te
chnique with I-125-labeled ET-I. Infarct rats developed MF with mild p
ulmonary 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 i
n lungs of HF rats (0.01+/-0.17 pg/mL). Plasma ET-I levels correlated
closely and inversely with ET-1 extraction (P<0.001). Conclusions-HF i
s associated with reduced pulmonary ET-I clearance that contributes to
the increase in circulating levels.