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Aspirin improves endothelial dysfunction in atherosclerosis
S Husain1, N P Andrews, D Mulcahy
1Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892-1650, USA.
Insights
Aspirin improves endothelial dysfunction in atherosclerosis by reversing a cyclooxygenase-dependent constricting factor, enhancing acetylcholine-mediated vasodilation and potentially reducing thrombosis.
Area of Science:
- Vascular Biology
- Pharmacology
- Cardiovascular Medicine
Background:
- Aspirin's benefits in atherosclerosis are linked to antiplatelet effects, but its impact on endothelial function is unclear.
- Endothelial dysfunction in atherosclerosis may involve a cyclooxygenase-dependent constricting factor.
- This study investigated aspirin's potential to reverse this dysfunction.
Purpose of the Study:
- To determine if aspirin can improve endothelial function in patients with atherosclerosis.
- To investigate the role of cyclooxygenase-dependent factors in aspirin's effects on vasodilation.
Main Methods:
- Vascular endothelial function was assessed using acetylcholine and substance P in patients with coronary atherosclerosis and healthy controls.
- Endothelium-independent function was tested with sodium nitroprusside.
- Measurements were taken before and after intravenous aspirin administration.
Main Results:
- Acetylcholine-induced vasodilation was impaired in patients with atherosclerosis compared to controls.
- Aspirin significantly improved acetylcholine-mediated vasodilation specifically in patients with atherosclerosis.
- No significant effects of aspirin were observed on responses to substance P or sodium nitroprusside.
Conclusions:
- A cyclooxygenase-dependent constrictor mechanism influences vasodilation in atherosclerosis.
- Aspirin can improve endothelial dysfunction by modulating this mechanism.
- This improvement may contribute to aspirin's beneficial effects in preventing atherosclerosis progression and thrombosis.
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.
Methods And 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.