Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.
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.
Asahi
T
T
Second Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus, Nishihara, Okinawa, Japan.
Shimabukuro
M
M
Oshiro
Y
Y
Yoshida
H
H
Takasu
N
N
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
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D014284:Triiodothyronine; D017315:Cilazapril; D011433:Propranolol