Effects of beta-receptor blockade and angiotensin II type I receptor antagonism in isoproterenol-induced heart failure in the rat.
The aim of this study was to examine the effects of both angiotensin II type I receptor antagonism using losartan (LOS) and beta-receptor blockade by metoprolol (MP) in isoproterenol-induced cardiac injury in the rat. Two weeks after isoproterenol (ISO) application, 90 ISO and 30 control (CTRL) rats were examined. ISO rats were treated for two weeks with either LOS, MP, or vehicle (n = 30 each group). Compared to CTRL, ISO induced left ventricular hypertrophy (LVH), fibrosis, and overexpression of extracellular matrix proteins. LOS significantly attenuated these changes. MP only reduced LVH, but exerted no effect on structural alterations. LV end-diastolic and mean right atrial pressures were significantly increased in the ISO group and normalized in the LOS and MP group. Mean aortic blood flow velocity was significantly decreased in the ISO group and unaltered in the LOS and MP group versus CTRL. Blood pressure was decreased in ISO and LOS rats. MP treatment had no effect on blood pressure, but significantly lowered heart rate. Isoproterenol induced mild heart failure. Losartan and metoprolol applications in ISO-treated rats were highly effective in attenuating hemodynamic alterations and LVH. Early application of losartan 24 hours after isoproterenol-induced cardiac injury revealed significant beneficial effects on myocardial structure.
Grimm
D
D
Institute of Clinical Pharmacology and Toxicology, UKBF FU Berlin, Germany. grimm@zedat.fu-berlin.de
Holmer
S R
SR
Riegger
G A
GA
Kromer
E P
EP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000187:drug effects; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D007545:Isoproterenol / Q000633:toxicity; D007797:Laminin / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008790:Metoprolol / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000318:Adrenergic beta-Agonists; D057911:Angiotensin Receptor Antagonists; D016326:Extracellular Matrix Proteins; D007797:Laminin; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011943:Receptors, Adrenergic, beta; D008790:Metoprolol; D019808:Losartan; D007545:Isoproterenol