Endothelin receptor blockade in canine oleic acid-induced lung injury.
OBJECTIVE
To investigate the effects of endogenous endothelins on pulmonary haemodynamics and gas exchange in oleic acid lung injury.


METHODS
Prospective experimental study in dogs.


METHODS
Animal research laboratory in a university teaching hospital. SUBJECTS. Seventeen anaesthetised and ventilated mongrel dogs.


METHODS
Nine pretreated dogs received an infusion of the endothelin A and B receptor antagonist bosentan (10 mg/kg) started before oleic acid. Eight treated dogs received bosentan started 90 min after oleic acid. Cardiac index (CI) was manipulated by inflating an inferior vena caval balloon or by opening a femoral arterio-venous bypass.


RESULTS
Pulmonary vascular resistance was defined by measuring the gradient between mean pulmonary artery pressure (MPAP) and occluded PAP (PAOP) at five levels of CI. Intrapulmonary shunt was measured using the inert gas SF(6). Pretreatment with bosentan prevented the oleic acid-induced shift of (MPAP-PAOP)/CI plots to higher pressures, but did not affect the increase in intrapulmonary shunt. Treatment of established oleic acid lung injury with bosentan had no effect.


CONCLUSIONS
Pretreatment, but not treatment, with bosentan, in the dose used, blunted the oleic acid-induced increase in pulmonary vascular resistance, suggesting that endothelins contribute to the increase in pulmonary vascular tone in the early stages of oleic acid lung injury.
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Ives
I
Hubloue
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Dominique
D
Biarent
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Sophia
S
Abdel Kafi
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Gilbert
G
Bejjani
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Christian
C
Mélot
Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium.
Robert
R
Naeije
Department of Intensive Care, Erasme University Hospital, 808 Lennik Road, 1070, Brussels, Belgium. marc.leeman@ulb.ac.be.|Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Erasme University Hospital, Brussels, Belgium. marc.leeman@ulb.ac.be.
Marc
M
Leeman
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077300:Bosentan; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D065128:Endothelin Receptor Antagonists; D007262:Infusions, Intravenous; D019301:Oleic Acid; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides; D019301:Oleic Acid; D000077300:Bosentan