Wexler B C
Atherosclerosis. 1981 May;39(2):253-66. doi: 10.1016/0021-9150(81)90075-7.
Male and female, Sprague-Dawley rats, with and without arteriosclerosis, were subjected to chronic treatment with furosemide for 4 weeks. Furosemide-treated rats manifested increased adrenal and kidney weights along with an increase in blood pressure; rats with pre-existing arteriosclerosis showed considerable reduction in heart and body weights. Furosemide-treated animals displayed an increase in circulating levels of creatine phosphokinase, lactic dehydrogenase, free fatty acids, glucose, BUN and uric acid. Circulating levels of triglycerides, total cholesterol, and corticosterone were subnormal, whereas aldosterone was distinctly elevated. Despite these metabolic derangements, de novo arterial disease did not appear in virgin rats without pre-existing arterial disease. However, furosemide-treated virgin rats did develop grossly visible apical and left-ventricular foci of myocardial necrosis, i.e., 12% in males, 9% in female virgins. Breeder rats with pre-existing arteriosclerosis manifested exacerbation of their arterial disease, e.g., intimal calcification of the epicardial coronary arteries along with foci of myocardial fibrosis and islet beta-cell granule depletion. Adrenocortical lipid alterations appeared in all animals treated with furosemide. It is suggested that this spectrum of metabolic and histopathologic degenerative changes may have been caused by secondary aldosteronism due to the chronic treatment with furosemide.
选用有或没有动脉硬化的雄性和雌性斯普拉格-道利大鼠，用速尿进行为期4周的慢性治疗。用速尿治疗的大鼠肾上腺和肾脏重量增加，同时血压升高；已有动脉硬化的大鼠心脏和体重显著减轻。用速尿治疗的动物循环中的肌酸磷酸激酶、乳酸脱氢酶、游离脂肪酸、葡萄糖、尿素氮和尿酸水平升高。甘油三酯、总胆固醇和皮质酮的循环水平低于正常，而醛固酮明显升高。尽管有这些代谢紊乱，但在没有原有动脉疾病的未交配大鼠中未出现新的动脉疾病。然而，用速尿治疗的未交配大鼠确实出现了肉眼可见的心肌坏死的心尖和左心室病灶，即雄性为12%，雌性未交配大鼠为9%。已有动脉硬化的繁殖大鼠其动脉疾病加重，例如心外膜冠状动脉内膜钙化，伴有心肌纤维化灶和胰岛β细胞颗粒减少。所有用速尿治疗的动物都出现了肾上腺皮质脂质改变。提示这种代谢和组织病理学退行性变化谱可能是由于用速尿进行慢性治疗导致的继发性醛固酮增多症引起的。
