Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism

Abstract

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 ETA receptor (ETA-R) antagonist in a rat model of APAE over 3h. APAE rats developed a higher right ventricular systolic pressure (RVSP), lower mean arterial blood pressure (MABP), and had lower PaO2. At 3h, 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 10–25min) of MABP without affecting the subsequent lowering of MABP, and improved oxygen saturation in APAE rats. These results show that ETA-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.