Acute cardiopulmonary effects of a dual-endothelin receptor antagonist on oleic acid-induced pulmonary arterial hypertension in dogs.

Abstract

The objective of this study was to evaluate the cardiopulmonary effects of a dual-endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n=6) received saline treatment, whereas the treatment group (n=6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous [i.v.]+1 mg/kg/h i.v. infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23 +/- 2 mm Hg to 15 +/- 2 mm Hg; P<.01) and a 22% decrease in PVR (from 860 +/- 105 dyn.s.cm(-5) to 670 +/- 96 dyn.s.cm(-5); P<.01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual-ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual-ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.

• Authors: Ling Wang, Du Ming Zhu, Xiao Su, Chun Xue Bai, Lorraine B Ware, Michael A Matthay
• Journal: Experimental lung research (Exp Lung Res) 2004 Jan-Feb Vol. 30 Issue 1 Pg. 31-42 ISSN: 0190-2148 [Print] England
• PMID: 14967602 (Publication Type: Journal Article)

Chemical References

• Endothelin Receptor Antagonists
• Pyridines
• Tetrazoles
• Vasodilator Agents
• Oleic Acid
• tezosentan
• Oxygen

Topics

• Acute Disease
• Animals
• Dogs
• Endothelin Receptor Antagonists
• Hypertension, Pulmonary (chemically induced, drug therapy)
• Oleic Acid
• Oxygen (metabolism)
• Pulmonary Artery (drug effects, physiology)
• Pulmonary Circulation (drug effects)
• Pulmonary Gas Exchange (drug effects)
• Pulmonary Veins (drug effects, physiology)
• Pyridines (pharmacology)
• Random Allocation
• Respiratory Mechanics (drug effects)
• Tetrazoles (pharmacology)
• Vasodilator Agents (pharmacology)