title: Aspirin improves endothelial dysfunction in atherosclerosis.
abstract: BACKGROUND
  The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. We hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action can be reversed by aspirin.
  
  
  RESULTS
  In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested femoral vascular endothelial function with acetylcholine and substance P and endothelium-independent function with sodium nitroprusside before and after intravenous aspirin. Drugs were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but not substance P-or sodium nitroprusside-induced vasodilation was lower in patients with atherosclerosis than in those with only risk factors. Aspirin had no baseline effect but improved acetylcholine-mediated vasodilation only in patients with atherosclerosis; at the peak dose, acetylcholine-mediated femoral vascular resistance index was 19 +/- 5%, P=.002 lower. There was a correlation between the baseline response to acetylcholine and the magnitude of improvement with aspirin (r=.5, P=.05). Thus, patients with a depressed response to acetylcholine had greater improvement with aspirin, and vice versa. The presence of atherosclerosis was an independent determinant of improvement with aspirin. Aspirin had no effect on the responses to either substance P or sodium nitroprusside.
  
  
  CONCLUSIONS
  Cyclooxygenase-dependent, endothelium-derived vasoconstrictor release modulates acetylcholine-induced peripheral vasodilation in patients with atherosclerosis. Improvement of endothelial dysfunction with aspirin may improve vasodilation, reduce thrombosis, and inhibit progression of atherosclerosis and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892-1650, USA.
authors.forename: S
authors.initials: S
authors.lastname: Husain
authors.forename: N P
authors.initials: NP
authors.lastname: Andrews
authors.forename: D
authors.initials: D
authors.lastname: Mulcahy
authors.forename: J A
authors.initials: JA
authors.lastname: Panza
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy*; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D015203:Reproducibility of Results; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D013373:Substance P; D000109:Acetylcholine; D001241:Aspirin