Pathogenic Role of Endothelin 1 in Hemodynamic Dysfunction in Experimental Acute Pulmonary Thromboembolism

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor a...

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Published in:American journal of respiratory and critical care medicine 2001-10, Vol.164 (7), p.1282-1287
Main Authors: LEE, JI-HYUN, CHUN, YONG-GAM, LEE, IN-CHUL, TUDER, RUBIN M, HONG, SANG-BUM, SHIM, TAE-SUN, LIM, CHAE-MAN, KOH, YOUNSUCK, KIM, WOO-SUNG, KIM, DONG-SOON, KIM, WON-DONG, LEE, SANG-DO
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Biological and medical sciences
Dogs
Endothelin-1 - physiology
Hemodynamics
Medical sciences
Pneumology
Pulmonary Embolism - pathology
Pulmonary Embolism - physiopathology
Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases
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Summary:The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ET(A) receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ET(A) receptor antagonists might constitute a useful therapeutic tool for APE.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.164.7.2011011