Evaluation of (1-sarcosine, 8-isoleucine) angiotensin II as a therapeutic agent for oleic acid-induced pulmonary edema

(1-Sarcosine, 8-isoleucine) angiotensin II was assessed as a therapeutic agent for acute respiratory distress syndrome with oleic acid pulmonary edema in sheep used as an experimental model. Under general anesthesia with controlled mechanical ventilation with 100% oxygen, 32 sheep received oleic acid (0.075 ml/kg) intravenously. After oleic acid infusion, 20 animals were treated with continuous intravenous infusion of the angiotensin II analogue; nine received 300 ng/kg/min, six received 600 ng/kg/min, and five received 2000 ng/kg/min. Cardiopulmonary measurements were repeated every 30 minutes for 270 minutes. According to time-integrated PaO₂, six of 15 animals of the groups given 300 and 600 ng/kg/min (43%) did not respond to the treatment. All animals responded in the group given 2000 ng/kg/min. Animals in the latter group had lower Q̇s/Q̇t, PaCO₂, and airway resistance than had the control animals. Elevation of pulmonary vascular resistance was limited and mean arterial blood pressure was well maintained. These results reveal that (1-Sar, 8-Ile) angiotensin II is effective in the treatment of oleic acid-induced pulmonary edema.