Nifedipine limits infarct size via NO-dependent mechanisms in dogs.
OBJECTIVE
Amlodipine increases NO levels in coronary vessels and aorta via bradykinin-dependent mechanisms in vitro. We have previously reported that nifedipine increases cardiac NO levels in the ischemic canine hearts, suggesting that nifedipine may also have protective effects against ischemia and reperfusion injury, because the enhancement of NO production limits infarct size. We tested whether nifedipine limits infarct size via NO-dependent mechanisms.


METHODS
In open chest dogs, the left anterior descending coronary artery was perfused with blood through a bypass tube and occluded for 90 min followed by 6 hours of reperfusion. Infarct size was assessed at 6 hours of reperfusion. Nifedipine of 3 or 6 microg/kg/min was infused into the bypass tube between 10 min prior to the onset of ischemia and 60 min of reperfusion.


RESULTS
Neither systemic blood pressure nor heart rate changed during infusion of nifedipine. Infarct size was reduced by the administration of nifedipine (3 or 6 microg/kg/min) compared with the untreated condition (25.6+/-2.6 and 19.1+/-3.5 vs. 43.4+/-5.6%, respectively), which was completely blunted by L-NAME (45.0+/-3.6 and 45.4+/-4.2 vs. 47.9+/-3.9% in the nifedipine (3 or 6 microg/kg/min) with L-NAME groups vs. the L-NAME group). Myeloperoxidase activity of the myocardium increased after 6 hours of reperfusion, which was attenuated by nifedipine. The limitation of infarct size and the attenuation in myeloperoxidase actiivity were completely blunted by L-NAME. There were no significant differences in collateral blood flow at 45 min of ischemia between each group.


CONCLUSIONS
We conclude that the Ca channel blocker, nifedipine, limits infarct size via NO-dependent mechanisms.
Asanuma
H
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Japan.
Kitakaze
M
M
Funaya
H
H
Takashima
S
S
Minamino
T
T
Node
K
K
Sakata
Y
Y
Asakura
M
M
Sanada
S
S
Shinozaki
Y
Y
Mori
H
H
Kuzuya
T
T
Tada
M
M
Hori
M
M
D000818:Animals; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation; D004285:Dogs; D004727:Endothelium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009195:Peroxidase; D009543:Nifedipine; D019331:NG-Nitroarginine Methyl Ester