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.