title: 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.
abstract: 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 1 (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 aspirintreated 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-1 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.
authors.affiliation: Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Via Enrico dal Pozzo, I-06126 Perugia, Italy. grespa@unipg.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Rino
authors.initials: R
authors.lastname: Migliacci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Procacci
authors.forename: Paola
authors.initials: P
authors.lastname: De Monte
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
mesh_terms: D000368:Aged; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D015444:Exercise; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000097:blood; D035002:Lower Extremity / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D019272:Leukocyte Elastase; C102148:nitroaspirin; D001241:Aspirin