Nicorandil decreases postischemic actin oxidation.
This study examined the hypothesis that preconditioning can decrease postischemic oxidative protein damage. Isolated rat hearts were subjected to 25 min of normothermic global ischemia followed by 45 min of reperfusion. These were compared with hearts pretreated with 20 microM nicorandil or preconditioned with two cycles of ischemia. Changes in the high energy phosphates, ATP and phosphocreatine, were followed using (31)P-NMR spectroscopy. Protein carbonyls were assessed using an immunoblot technique. Postischemic hemodynamic function and high energy phosphates recovered to significantly (p <.05) higher levels in nicorandil-treated and ischemic preconditioned hearts as compared to controls. Postischemic protein carbonyl formation was highest in control reperfused hearts but reduced to intermediate between control and preischemic hearts by ischemic preconditioning and virtually prevented by nicorandil pretreatment, with a prominent band at 43 kDa significantly affected (p <.05). Based on immunoshift and immunoprecipitation studies, this band was identified as a mixture of actin isoforms. These studies support the conclusion that nicorandil diminishes protein oxidative damage in general, and specifically actin oxidation, which in the presence of improved supply of high energy phosphates, leads to enhanced postischemic contractile function.
Schwalb
H
H
The Joseph Lunenfeld Cardiac Surgery Research Center, Kiryat Hadassah, Jerusalem, Israel.
Olivson
A
A
Li
J
J
Houminer
E
E
Wahezi
S E
SE
Opie
L H
LH
Maulik
D
D
Borman
J B
JB
Powell
S R
SR
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000517:prevention & control; D020108:Nicorandil / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D000889:Anti-Arrhythmia Agents; D005609:Free Radicals; D020108:Nicorandil