Effects of ACE inhibition and beta-blockade on collagen remodelling in the heart of Bio 14.6 hamsters.
1. The effects of angiotensin converting enzyme (ACE) inhibition and beta-blockade on collagen in the heart and on plasma catecholamines and tissue angiotensin (Ang) I and II were examined in Bio 14.6 Syrian hamsters. Male hamsters (76-79 days old) were given low-dose enalapril (3 mg/kg per day), high-dose enalapril (30 mg/kg per day), atenolol (50 mg/kg per day) or vehicle for 65 days. Age and sex matched healthy F1b hamsters were used as controls. Collagen concentration was determined by measuring hydroxyproline content and the relative proportion of type I, III, and V collagens was obtained by non-interrupted sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). Per cent collagen area (PCA) was measured by pixel counting in myocardial tissue by a personal computer. 2. Although heartweight (HW) and bodyweight (BW) in F1b controls were significantly higher compared with drug-treated groups and vehicles, the HW/BW ratio in cardiomyopathic Bio 14.6 hamsters tended to be high compared with F1b controls and was decreased by each drug treatment. 3. Collagen concentration, total collagen content and PCA in the heart of Bio 14.6 hamsters were significantly higher than F1b controls. Collagen concentration and total collagen content were significantly decreased in all drug-treated groups compared with vehicles. 4. The proportion of type I collagen tended to decrease while that of type III collagen tended to increase in all drug-treated groups compared with vehicles. Type V collagen in vehicle-treated group was significantly higher than in F1b controls, while it tended to decrease in all drug-treated groups compared with vehicles. 5. Plasma concentrations of catecholamines (adrenaline and noradrenaline) were decreased significantly by atenolol and high-dose enalapril, but not by low-dose enalapril. Tissue AngI remained unaltered in any of the drug-treated hamsters. Tissue AngII was decreased by the high-dose enalapril and beta-blockade, and tended to be decreased by low-dose enalapril treatment. 6. These results reveal that enalapril and atenolol produced similar beneficial effects on collagen remodelling in Bio 14.6 hamsters by decreasing the total amount of collagen, and also by changing collagen phenotypes through the inhibition of the renin-angiotensin system. Both drugs also improved myocardial morphological integrity.
Mansoor
A M
AM
Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Honda
M
M
Kuramochi
T
T
Tanaka
K
K
Morioka
S
S
Takabatake
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D003094:Collagen / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000187:drug effects*; D008297:Male
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D001262:Atenolol; D004656:Enalapril; D003094:Collagen; D004837:Epinephrine