Furosemide-induced hyperuricemia, hyperglycemia, hypertension and arterial lesions in nonarteriosclerotic and arteriosclerotic rats.
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.
D000818:Animals; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006943:Hyperglycemia / Q000209:etiology*; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000033:anatomy & histology; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D014527:Uric Acid / Q000097:blood*
D001786:Blood Glucose; D008055:Lipids; D014527:Uric Acid; D005665:Furosemide; D003402:Creatine Kinase; D003345:Corticosterone