Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism.
Acute pulmonary air embolism (APAE) injures the vascular endothelium in the lung and results in pulmonary hypertension (PH). Endothelins (ETs), a family of potent vasoactive peptides, are known to be associated with PH of various aetiologies. We evaluated the effects of ABT-627, a selective ET(A) receptor (ET(A)-R) antagonist in a rat model of APAE over 3 h. APAE rats developed a higher right ventricular systolic pressure (RVSP), lower mean arterial blood pressure (MABP), and had lower PaO(2). At 3 h, arterial plasma levels of ET-1 were increased. ABT-627-treated controls showed no effects. However, ABT-627 significantly lowered RVSP during APAE, abolished the short recovery phase (within 10-25 min) of MABP without affecting the subsequent lowering of MABP, and improved oxygen saturation in APAE rats. These results show that ET(A)-R subtype is involved in the pathogenesis of APAE since a blockade of this receptor subtype attenuated the cardiopulmonary deterioration and improved blood gas exchanges in rats with this disease.
Laval Hospital Research Center, Quebec Heart & Lung Institute, Department of Medicine, Laval University, 2725 Chemin Ste-Foy, Ste-Foy, QC G1V 4G5, Canada.
Bilal
B
Ayach
John
J
Tsang
Arco Y
AY
Jeng
André
A
Blouin
Mélanie
M
Gosselin
Fu-Hou
FH
Wang
Jinshyun R
JR
Wu-Wong
Jerry
J
Wessale
Terry J
TJ
Opgenorth
Bruno
B
Battistini
D000208:Acute Disease; D000818:Animals; D000077868:Atrasentan; D004618:Embolism, Air / Q000188:drug therapy / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D019334:Endothelin-3 / Q000235:genetics; D015870:Gene Expression; D008168:Lung / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D010100:Oxygen; D000077868:Atrasentan