In vivo reduction of reperfusion injury to the heart with apelin-12 peptide in rats.
Apelin-12 (A-12) peptide was synthesized by automated solid phase method and purified by reverse phase HPLC. Its homogeneity and structure were confirmed by HPLC, (1)H-NMR spectroscopy, and mass spectroscopy. Acute myocardial infarction was induced by 40-min occlusion of the left coronary artery with subsequent 60-min reperfusion in narcotized Wistar rats. Peptide A-12 was injected (intravenous bolus, 0.07 or 0.35 μmol/kg) to experimental animals simultaneously with the beginning of reperfusion. Injections of A-12 in these doses led to reduction of systolic BP to 67 and 85% of the initial level, respectively, which was virtually restored completely by the end of reperfusion, and to a significant reduction of the infarction focus in the myocardium (by 21 and 34% in comparison with the control, respectively). Injection of A-12 in a dose of 0.35 μmol/kg led to reduction of plasma concentrations of necrosis markers in comparison with the control by the end of reperfusion: MB-creatine kinase by 56%, lactate dehydrogenase by 30%. The results attest to vasodilatory effects of A-12 under conditions of heart reperfusion in vivo; the peptide injected after local ischemia limits the myocardial infarction size and reduces damage to cardiomyocyte membrane.
Russian Cardiology Research-and-Production Complex, Rosmedtechnologies, Moscow, Russia. olpi@cardio.ru
O I
OI
Pisarenko
L I
LI
Serebryakova
Yu A
YA
Pelogeykina
I M
IM
Studneva
D N
DN
Khatri
O V
OV
Tskitishvili
Zh D
ZhD
Bespalova
A A
AA
Az'muko
M V
MV
Sidorova
M E
ME
Pal'keeva
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D052279:Creatine Kinase, MB Form / Q000097:blood; D006352:Heart Ventricles / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D009566:Nitrates; D009573:Nitrites; C495200:apelin-12 peptide; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form