Aldosterone Administration to Mice Stimulates Macrophage NADPH Oxidase and Increases Atherosclerosis Development

Abstract

Background— The renin-angiotensin-aldosterone system is involved in the pathogenesis of atherosclerosis, partially because of its pro-oxidative properties. We questioned the effect and mechanisms of action of administration of aldosterone to apolipoprotein E–deficient (E0) mice on their macrophages and aorta oxidative status and the ability of pharmacological agents to block this effect. Methods and Results— Aldosterone (0.2 to 6 μg · mouse−1 · d−1) was administered to E0 mice alone or in combination with eplerenone (200 mg · kg−1 · d−1), ramipril (5 mg · kg−1 · d−1), or losartan (25 mg · kg−1 · d−1). Mouse aortic atherosclerotic lesion area and macrophage and aortic oxidative status were evaluated. Aldosterone administration enhanced the mouse atherosclerotic lesion area by 32%. Mouse peritoneal macrophages and aortic segments from aldosterone-treated mice exhibited increased superoxide anion formation by up to 155% and 69%, respectively, and this effect was probably mediated by NADPH oxidase activation,...