Chronic toxicity and carcinogenicity studies with the ?-adrenoceptor antagonist levobunolol*1

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.

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Uterine Fibroids: The Elephant in the Room

Walker

Stewart

2005

Science

499

374

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Chronic toxicity and carcinogenicity studies with the ?-adrenoceptor antagonist levobunolol*1

Cited by 3 publications

References 8 publications

Update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals

Update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals

Oxygen Radical System in Chronic Infarcted Rat Heart: The Effect of Combined Beta Blockade and ACE Inhibition

Uterine Fibroids: The Elephant in the Room

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