title: Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.
abstract: We evaluated the effects of hyperthyroidism on cardiac structural changes and postischemic myocardial function, and also studied how an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, can alter these changes. Hyperthyroidism was induced by daily intraperitoneal injection of thyroxine (T4) (600 microg/kg) with or without cilazapril (10 mg/kg per day, orally), and control rats were given by vehicle. After 2 weeks of treatment, T4-treated rats showed increases in blood pressure and heart weight to body weight ratio (HW:BW). Cilazapril decreased blood pressure to control values and reduced HW:BW. In the isolated working heart preparation, T4-treated rats showed a poor postischemic recovery of left ventricular pressure-rate product (14% of baseline at 30 minutes of reperfusion vs. vehicle 85%) and cardiac work (6% vs. 71%). Cilazapril recovered both values to 49% and 43%. Propranolol (500 mg/L in drinking water) decreased blood pressure to the same extent as cilazapril in hyperthyroid rats, but changed neither HW:BW nor the postischemic myocardial dysfunction. Percent recovery of cardiac work was inversely well correlated with HW:BW (R2 = 0.998, p < 0.001). Results indicate that T4-induced cardiac hypertrophy enhances postischemic cardiac dysfunction. Results also indicate renin-angiotensin system (RAS), but not sympathetic nerve activation, is involved in cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Asahi
authors.forename: M
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Y
authors.initials: Y
authors.lastname: Oshiro
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Takasu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D048429:Cell Size; D017315:Cilazapril / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006980:Hyperthyroidism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D014284:Triiodothyronine; D017315:Cilazapril; D011433:Propranolol