Enhancement of myocardial reactive hyperemia with manganese-superoxide dismutase: role of endothelium-derived nitric oxide.
OBJECTIVE
To test the hypothesis that superoxide radicals generated during myocardial ischemia and reperfusion influence reactive hyperemia (RH) by reacting with endothelium-derived nitric oxide (EDNO), we examined the effect of manganese (Mn)-superoxide dismutase (SOD) on RH in anesthetized dogs.


METHODS
Twelve dogs were pretreated with 8-phenyltheophylline (8PT) to block adenosine's effect. Five dogs were pretreated with 8PT and NG-nitro-L-arginine methyl ester (L-NAME) to block adenosine's and EDNO's effects. Following occlusion of the left circumflex artery (LCX) for 10 and 60 s, RH was observed before and after Mn-SOD. In another group of 6 dogs pretreated with 8PT, RH following 60-s LCX occlusion was observed before and after Mn-SOD and catalase. For comparison with the effect of Mn-SOD, that of copper, zinc (Cu,Zn)-SOD was also examined in another group of 5 dogs.


RESULTS
In the dogs pretreated with 8PT, Mn-SOD significantly increased excess flow and repayment of flow debt during RH after 60-s LCX occlusion but did not affect RH after 10-s LCX occlusion. Mn-SOD-induced augmentation of RH following 60-s LCX occlusion was not affected by catalase, while it was completely abolished by L-NAME. In contrast to Mn-SOD, Cu,Zn-SOD showed no effect on RH following 60-s LCX occlusion in the dogs pretreated with 8PT.


CONCLUSIONS
Superoxide radicals generated during ischemia for 60 s and reperfusion attenuates myocardial RH through inactivation of EDNO. Mn-SOD shows more beneficial effects on myocardial RH than Cu,Zn-SOD.
Tsunoda
R
R
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Okumura
K
K
Ishizaka
H
H
Matsunaga
T
T
Tabuchi
T
T
Tayama
S
S
Yasue
H
H
D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D008345:Manganese; D001120:Arginine; D013806:Theophylline; C028322:8-phenyltheophylline; D002374:Catalase; D013482:Superoxide Dismutase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester