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 typ e I receptor antagonism using losartan (LOS) and beta-receptor blockade by metoprolol (MP) in isoproterenol-induced cardiac injury in the rat. Two wee ks 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 ventricula r hypertrophy (LVH), fibrosis, and overexpression of extracellular matrix p roteins. LOS significantly attenuated these changes. MP only reduced LVH, b ut exerted no effect on structural alterations. LV end-diastolic and mean r ight atrial pressures were significantly increased in the ISO group and nor malized in the LOS and MP group. Mean aortic blood flow velocity was signif icantly decreased in the ISO group and unaltered in the LOS and MP group ve rsus CTRL. Blood pressure was decreased in ISO and LOS rats. MP treatment h ad no effect on blood pressure, but significantly lowered heart rate. Isopr oterenol induced mild heart failure. Losartan and metoprolol applications i n ISO-treated rats were highly effective in attenuating hemodynamic alterat ions and LVH. Early application of losartan 24 hours after isoproterenol-in duced cardiac injury revealed significant beneficial effects on myocardial structure. (C) 1999 Elsevier Science Inc.