Angiotensin II-induced pulmonary edema in a rabbit model.
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 signficantly 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.
Yamamoto
T
T
Department of Preventive Medicine, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Japan.
Wang
L
L
Shimakura
K
K
Sanaka
M
M
Koike
Y
Y
Mineshita
S
S
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D019808:Losartan; D008297:Male; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan