Am. Mansoor et al., EFFECTS OF ACE-INHIBITION AND BETA-BLOCKADE ON COLLAGEN REMODELING INTHE HEART OF BIO-14.6 HAMSTERS, Clinical and experimental pharmacology and physiology, 23(1), 1996, pp. 43-49
1. The effects of angiotensin converting enzyme (ACE) inhibition and b
eta-blockade on collagen in the heart and on plasma catecholamines and
tissue angiotensin (Ang)I and II were examined in Bio 14.6 Syrian ham
sters. 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 F(1
)b hamsters were used as controls. Collagen concentration was determin
ed by measuring hydroxyproline content and the relative proportion of
type I, III, and V collagens was obtained by non-interrupted sodium do
decyl polyacrylamide gel electrophoresis (SDS-PAGE), Per cent collagen
area (PCA) was measured by pixel counting in myocardial tissue by a p
ersonal computer. 2. Although heartweight (HW) and bodyweight (BW) in
F(1)b controls were significantly higher compared with drug-treated gr
oups and vehicles, the HW/BW ratio in cardiomyopathic Bio 14.6 hamster
s tended to be high compared with F(1)b 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 t
han F(1)b 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 whil
e that of type III collagen tended to increase in all drug-treated gro
ups compared with vehicles. Type V collagen in vehicle-treated group w
as significantly higher than in F(1)b controls, while it tended to dec
rease in all drug-treated groups compared with vehicles, 5. Plasma con
centrations of catecholamines (adrenaline and noradrenaline) were decr
eased significantly by atenolol and high-dose enalapril, but not by lo
w-dose enalapril. Tissue AngI remained unaltered in any of the drug-tr
eated hamsters. Tissue AngII was decreased by the high-dose enalapril
and betablockade, and tended to be decreased by low-dose enalapril tre
atment, 6. These results reveal that enalapril and atenolol produced s
imilar beneficial effects on collagen remodelling in Bio 14.6 hamsters
by decreasing the total amount of collagen, and also by changing coll
agen phenotypes through the inhibition of the renin-angiotensin system
, Both drugs also improved myocardial morphological integrity.