Chemical preconditioning with 3-nitropropionic acid in hearts: role of mitochondrial K(ATP) channel.
We investigated the cardioprotective effect of 3-nitropropionic acid (3-NPA), an inhibitior of mitochondrial succinate dehydrogenase, and we wanted to show whether this protection is mediated by of opening mitochondrial ATP-sensitive potassium (K(ATP)) channels. Adult rabbits were treated with either 3-NPA (3 mg/kg iv) or saline (n = 6 rabbits/group). After 30 min (for early phase) or 24 h (for late phase) of the treatment, the animals were subjected to 30 min of ischemia and 3 h of reperfusion (ischemia-reperfusion). 5-Hydroxydecanoate (5-HD, 5 mg/kg iv),the mitochondrial K(ATP) channel blocker, was administered 10 min before ischemia-reperfusion in the saline- and 3-NPA-treated rabbits. 3-NPA caused a decrease in the infarct size from 27.8 +/- 4.2% in the saline group to 16.5 +/- 1.0% in the 3-NPA-treated rabbits during early phase and from 30.4 +/- 4.2% in the saline group to 17.6 +/- 1.05 in the 3-NPA group during delayed phase (P < 0.05, % of risk area). The anti-infarct effect of 3-NPA was blocked by 5-HD as shown by an increase in infarct size to 33 +/- 2.7% (early phase) and 31 +/- 2.4% (delayed phase) (P < 0.05 vs. 3-NPA groups). 5-HD had no proischemic effect in control animals. Also, 3-NPA had no effect on systemic hemodynamics. We conclude that 3-NPA induces long-lasting anti-ischemic effects via opening of mitochondrial K(ATP) channels.
Ockaili
R A
RA
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Bhargava
P
P
Kukreja
R C
RC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure; D003652:Decanoic Acids / Q000494:pharmacology; D006339:Heart Rate; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality; D009206:Myocardium / Q000378:metabolism; D009574:Nitro Compounds; D010085:Oxidative Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D011817:Rabbits; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D009574:Nitro Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011422:Propionates; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid