Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication

Summary

Ischemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day I (pre-treatment: aspirin = 3.1 ± 0.5%, nitroaspirin = 3.9 ± 0.7%, p=NS), and on day 28 (aspirin = 3.4 ± 0.7%, NCX 4016 = 3.2 ± 0.6%, p=NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = –1.15%, nitroaspirin = –1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirin-treated group (- 1.46%) while it was abolished in the NCX 4016-treated group (+ 0.79%, p= 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-l which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.

Keywords

Flow-mediated vasodilation - intermittent claudication - ischemia/reperfusion injury - nitric oxide

• References

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