Protective effects of dilazep and its novel derivative, K-7259, on mechanical and metabolic derangements induced by hydrogen peroxide in the isolated perfused rat heart.
The effect of dilazep, a potentiator of the adenosine-mediated effects, on the hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in the isolated rat heart, and compared with that of K-7259, a dilazep derivative having less potentiating action on the adenosine-mediated effects. The heart was perfused aerobically by Langendorff's technique at a constant flow and driven electrically. H2O2 (600 microM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure in the heart (i.e, mechanical dysfunction), decreased the tissue ATP level and increased the tissue AMP level (i.e., metabolic change) and increased the tissue level of malondialdehyde (i.e., lipid peroxidation). These mechanical and metabolic alterations induced by H2O2 were attenuated by dilazep (1 microM), and the effect of dilazep was not modified by 8-(p-sulfophenyl)-theophylline (20 microM), a nonselective adenosine receptor antagonist. K-7259 (1 microM) also attenuated the H2O2-induced mechanical and metabolic derangements. Nevertheless, neither dilazep nor K-7259 modified the tissue malondialdehyde level, which was increased by H2O2, and the mechanical function and energy metabolism of the normal (H2O2-untreated) heart. These results suggest that both dilazep and K-7259 attenuate mechanical and metabolic derangements induced by H2O2. The protective action of dilazep and K-7259 on the H2O2-induced derangements is not due to potentiation of adenosine-mediated effects, reduction of lipid peroxidation or preservation of energy.
Hara
A
A
Department of Pharmacology, Asahikawa Medical College, Japan.
Abiko
Y
Y
D000818:Animals; D004109:Dilazep / Q000031:analogs & derivatives* / 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; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
C092019:K 7259; D014665:Vasodilator Agents; D006861:Hydrogen Peroxide; D004109:Dilazep