Pulmonary Edema Induced by Angiotensin II in Rats

Abstract

ABSTRACT-Weperformed this study to demonstrate the experimental procedure for inducing pulmonary edema by angiotensin II (AT II) in rats and to determine the mechanism of hemodynamic pulmonary edema. In the pilot study, 10 pg/ml of AT II was found to be adequate as the edematogenic dose for inducing pulmonary edema. The edematogenic dose of AT II was intravenously given to rats pretreated with 20 mg/kg of an AT II-receptor antagonist, E 4177 (3-[(2"-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H-imidazo [4,5-b]pyridine), and to rats given 10 mg/kg of an alpha-adrenergic blocker, phentolamine. Similarly, pulmonary edema was induced by 25 tcg/ml of adrenaline in rats pretreated with E 4177 (20 mg/kg) and rats with no pretreatment. E 4177 completely suppressed the development of AT II-induced pulmonary edema, whereas phentolamine could not. On the contrary, E 4177 could not suppress the development of adrenaline-induced pulmonary edema. We concluded that AT II-induced pulmonary edema will develop via the specific AT II receptor without the indirect action of adrenaline.Keywords: Pulmonary edema, Angiotensin II, Adrenaline, Angiotensin II-receptor antagonist, PhentolamineHeart failure causes an increase in systemic vascular resistance and an accumulation of excess fluid as the compensatory adaptations of enhanced activities of the sympathetic nervous system and the renin-angiotensin system. The clinical features relating to pulmonary edema arise in the end-stage of the left ventricular failure due to the excessive compensatory adaptations.Angiotensinconverting enzyme inhibitors have currently attracted the attention of physicians as effective drugs that improve the prognostic outcomes of patients with heart failure (1). Since the drugs suppress the production of angiotensin II (AT II) which has a vigorously vasoconstrictive effect, they bring about a favorable clinical course in those patients. Although many studies have established experimentally that high doses of adrenaline, one of the most powerful cardiac stimulants, induce pulmonary edema as the result of increased afterload in systemic circulation which elevates the left atrial pressure (2), there are no reports to our knowledge, on the experimental induction of pulmonary edema by AT II. In the course of the study on pulmonary edema, we had been concerned with the vasoconstrictive effect of AT II and found that the bolus intravenous injection of AT II also induced pulmonary edema in rats. We therefore undertook the present study for the following reasons: 1) to propose the experimental procedure for inducing pulmonary edema by the administration of AT II in rats and 2) to determine the mechanism of AT II-induced pulmonary edema and the protective measures against it. MATERIALS AND METHODS Animals and outline of the experimentMale albino rats of the Wistar strain (n=57) weighing 250-300 g were purchased from Saitama Animal Lab.(Saitama) and housed under controlled conditions for at least two weeks before the experiments. They were randomly divided into...

Rapid Improvement of Acute Pulmonary Edema with Angiotensin Converting Enzyme Inhibitor under Hemodialysis in a Patient with Renovascular Disease

“…If bilateral renal artery stenosis, or an abnormal contralateral kidney exists, this does not happen and volume overloading can be induced (2, 3), possibly leading to the increased cardiac afterload and APE. It was demonstrated that intravenous angiotensin II injection could produce APE in rats (8) and rabbits (9), possibly as a result of increasing cardiac afterload. However, patients with renovascular disease could experience ‘flash’ pulmonary edema without left ventricular dysfunction (4, 5).…”

Hypoxia modeling techniques: A review

“…Edematogenous dose of AT-II is administered intravenously to rats. A 10 μg/ml solution of angiotensin II (AT-II) in saline pH 6–7 at 1 ml/kg is a sufficient edematogenous dose to induce pulmonary edema in rats [ 113 ].…”