Effects of N-(2-mercaptopropionyl)-glycine on mitochondrial function in ischemic-reperfused heart.
OBJECTIVE
A possible mechanism for N-(2-mercaptopropionyl)-glycine (MPG) underlying the improvement of contractile function and mitochondrial activity of ischemic-reperfused rat hearts was examined.


METHODS
Isolated, perfused hearts were subjected to 35 min ischemia-60 min reperfusion. At the end of ischemia or reperfusion, myocardial Na(+) content and mitochondrial oxygen consumption rate (OCR) were examined. The perfused heart was treated with 0.1-1 mM MPG for 30 min prior to ischemia or for the first 30 min of reperfusion.


RESULTS
Ischemia increased myocardial Na(+) content (sodium overload) and decreased mitochondrial OCR. The left ventricular developed pressure (LVDP) of the untreated heart recovered to 19.8+/-3.8% of the preischemic value and the infarct area amounted to 23.3+/-1.7% of the left ventricle. The thiobarbiturate-reacting substance (TRS) was also increased in the reperfused, but not ischemic, myocardium. Pretreatment of the perfused heart with 0.3-1 mM MPG attenuated the ischemia-induced sodium overload and decrease in the OCR. Pretreatment with the agent also enhanced the postischemic recovery of LVDP, attenuated reperfusion-induced increase in TRS, and reduced the infarct area. Although the postischemic treatment with MPG suppressed the increase in TRS in the reperfused myocardium, a LVDP recovery of reperfused hearts was not observed. Cardiac mitochondria were isolated and examined for the direct effect of MPG on their function. Incubation with either 12.5 mM sodium lactate or 1 microM phenylarsine oxide neither altered the mitochondrial membrane potential nor induced mitochondrial swelling, whereas incubation with a combination of these agents elicited the membrane potential depolarization and swelling. Incubation of mitochondria with 1 mM MPG attenuated these events.


CONCLUSIONS
These results suggest that both attenuation of sodium overload and preservation of the mitochondrial function may largely contribute to cardioprotection of MPG in the ischemic-reperfused heart.
Tanonaka
Kouichi
K
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Iwai
Takeshi
T
Motegi
Kanataka
K
Takeo
Satoshi
S
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009924:Organ Culture Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D002316:Cardiotonic Agents; C110658:N-(2-mercaptoproprionyl)-glycine; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D012964:Sodium; D003402:Creatine Kinase; D005998:Glycine