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.
Akahira
M
M
Department of Pharmacology, Asahikawa Medical College, Nishikagura, Japan.
Hara
A
A
Hashizume
H
H
Nakamura
M
M
Abiko
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D015425:Myocardial Reperfusion; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D006861:Hydrogen Peroxide; D011224:Prazosin