Jpn. J. Pharmacol. 73 (1), 33-40 (1997)

Angiotensin II-Induced Pulmonary Edema in a Rabbit Model

Takatsugu Yamamoto (1), Li-man Wang (1), Kazuro Shimakura (2), Masaki Sanaka (1,#), Yuichi Koike (1) and Satoru Mineshita (1)

(1) Department of Preventive Medicine, Division of Social Medicine, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan
(2) Department of Surgery, Teikyo University School of Medicine, Mizonokuchi Branch, Kawasaki 213, Japan
(#) Present address: First Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173, Japan

Abstract: We conducted the present study to propose a rabbit model of pulmonary edema (PE) induced by angiotensin II (AII) and to test the preventive effect of losartan on this form of PE. AII was administered to rabbits intravenously at 50, 100, 150 or 300 microg/kg, either by continuous infusion (10 min) or by bolus injection (30 sec). Continuously administered AII (150 microg/kg) induced PE in most cases, while a bolus injection of the same dosage did not. Additionally, the incidence of PE increased with higher dosages of AII when it was infused continuously. A newly established parameter, the area under the systolic blood pressure-time curve corrected by baseline (cAUC), was prone to rise as the incidence of PE increased. Moreover, cAUC significantly correlated with the wet-dry lung weight ratio (r = 0.66, P < 0.05). Subsequently, 0.5 or 3.0 mg/kg of losartan was given before continuous infusion of 150 microg/kg of AII. The higher dosage of losartan prevented PE completely, while the lower one did so moderately. We concluded that intravenous administration of AII induces PE, probably as a result of increasing afterload. Furthermore, an adequate dosage of losartan can prevent PE because it reduces the pressor effect of AII.

Keywords: Angiotensin lI, Pulmonary edema, Heart failure, Afterload, Losartan

Copyrightę The Japanese Pharmacological Society 1997

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