Effect of endogenous nitric oxide on energy metabolism of rat heart mitochondria during ischemia and reperfusion.
The effects of ischemia and postischemic reperfusion on the functions of the heart and its mitochondria were studied with special attention to the effect of nitric oxide (NO) by treatment of rat hearts with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or its noninhibitory isomer N(G)-nitro-D-arginine methyl ester (D-NAME). NO generated during reperfusion caused increase in coronary flow (CF), but had no effect on the left ventricular pressure (LVP) or heart rate (HR). The ATP level of the heart decreased during ischemia and was not completely restored by introduction of oxygen during reperfusion due to damage of complexes I and II of the respiratory chain of mitochondria by NO. Inhibition of the respiratory chain resulted in generation of hydrogen peroxide, and NO and NO-derived species generated after production of NO caused further damage of various proteins in mitochondria, such as complexes I and II of the respiratory chain and pyruvate dehydrogenase (PDH). These results suggested that NO generated on reperfusion was the primary cause of mitochondrial dysfunction by damage of complexes I and II of the respiratory chain, with consequent increase of CF in the heart.
Abe
K
K
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Hayashi
N
N
Terada
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester