Protective effect of prazosin on the hydrogen peroxide-induced derangements in the isolated perfused rat heart.

The effect of prazosin, an alpha1-selective adrenoceptor antagonist, on the hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in the isolated rat heart, which was perfused aerobically by the Langendorffs technique at a constant flow rate and driven electrically. H2O2 (600 microM) produced both mechanical dysfunction (e.g., increase in the left ventricular end-diastolic pressure) and metabolic damage (e.g., decrease in the level of adenosine triphosphate) associated with lipid peroxidation (e.g., increase in the level of malondialdehyde). The H2O2-induced mechanical and metabolic derangements were attenuated by 2.5, 5, or 10 microM prazosin, and the increase in the level of malondialdehyde was attenuated by 5 or 10 microM prazosin. Nevertheless, prazosin had practically no effects on the mechanical function and energy metabolism of the H2O2-untreated normal heart at 2.5 or 5 microM, although it reduced the mechanical function at 10 microM. Prazosin was shown to have a hydroxyl radical scavenging effect. These results suggest that prazosin attenuates the H2O2-induced mechanical and metabolic derangements probably because of attenuation of the H2O2-induced lipid peroxidation in the heart.