Oxygen radical system in chronic infarcted rat heart: the effect of combined beta blockade and ACE inhibition.
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.
Theres
H
H
Medizinische Klinik und Poliklinik, Humboldt-Universität zu Berlin, Germany.
Wagner
K D
KD
Schulz
S
S
Strube
S
S
Leiterer
K P
KP
Romberg
D
D
Günther
J
J
Scholz
H
H
Baumann
G
G
Schimke
I
I
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D005979:Glutathione Peroxidase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase