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
Copyright© The Japanese Pharmacological Society 1997
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