Vascular tolerance to nitroglycerin in ascorbate deficiency: results are in favour of an important role of oxidative stress in nitrate tolerance: reply

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Abstract
In their comment to our recent study on the development of vascular tolerance to nitroglycerin (GTN) upon long-term ascorbate deprivation of guinea pigs,1 Daiber and Gori suggest that our data are in favour of an important role of oxidative stress in nitrate tolerance.2 We wish to point out that this issue was not a major focus of our study and cannot be decided in the absence of additional data, in particular measurements of vascular stress parameters. Nevertheless, unlike Daiber and Gori, we do not think that our results support the oxidative stress hypothesis of nitrate tolerance in this experimental model. As discussed in the paper, we are well aware of the limitations of the polyethylene glycol-conjugated superoxide dismutase/catalase experiments (which were requested by a reviewer of the paper), but the lack of effect of these widely applied scavenging enzymes is only one out of several observations seriously questioning the involvement of superoxide in vascular nitrate tolerance induced by ascorbate deficiency.