Age dependence of the cardiac lesions induced by minoxidil in the rat.
To evaluate the age- and dose-dependence of the cardiotoxicity induced by minoxidil, histologic studies were made of the hearts of 3-, 6-, 15- and 24-month-old Sprague Dawley rats treated with either 10, 50 or 250 mg/kg of the drug p.o. daily for two consecutive days. The 10 mg/kg dose of minoxidil induced myocyte necrosis in each of the 24-month-old rats but only in one other animal (6-month-old). The 50 mg/kg dose produced necrosis in all the 15- and 24-month-old rats, but in only one of the other animals (6-month-old), while the 250 mg/kg dose induced necrosis in animals of all ages. Inflammation was present in all minoxidil-treated animals, but at each dose level it was most severe in the oldest rats. Interstitial hemorrhages were observed at all dose levels, but increased in frequency and severity with the dose of minoxidil, and at each dose level they were more severe in the oldest animals. Vascular lesions consisting of arteriolar damage and calcification were observed only in the 24-month-old animals. Thus, these data demonstrate that the cardiac lesions induced by minoxidil are more frequent and severe in older than in younger rats.
Herman
E H
EH
Division of Research and Testing, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, MD 20708, USA.
Zhang
J
J
Chadwick
D P
DP
Ferrans
V J
VJ
D000375:Aging / Q000473:pathology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001167:Arteritis / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced; D008297:Male; D008914:Minoxidil / Q000633:toxicity*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000633:toxicity*
D014665:Vasodilator Agents; D008914:Minoxidil