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Assessing Endothelial Vasodilator Function with the Endo-PAT 2000
Published on: October 15, 2010
Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease:
Thomas Heitzer1, Volker Rudolph, Edzard Schwedhelm
1Universitäres Herzzentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf, Germany. heitzer@uke.uni-hamburg.de
Insights
Clopidogrel enhances nitric oxide bioavailability and reduces oxidative stress and inflammation in coronary artery disease patients. This suggests vasoprotective effects beyond its antiplatelet action.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Platelet activation contributes to clot formation, inflammation, and vascular injury.
- Symptomatic coronary artery disease (CAD) patients often have impaired endothelial function.
- Investigating clopidogrel's impact on endothelial nitric oxide (NO) bioavailability, oxidative stress, and inflammation in CAD is crucial.
Purpose of the Study:
- To evaluate the effects of clopidogrel on endothelial nitric oxide (NO) bioavailability.
- To assess clopidogrel's impact on oxidative stress markers.
- To determine clopidogrel's influence on inflammatory status in patients with symptomatic coronary artery disease.
Main Methods:
- 103 patients with symptomatic CAD on aspirin were randomized to clopidogrel or placebo.
- Forearm blood flow (FBF) responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were measured.
- Biomarkers of oxidative stress (8-iso-prostaglandin F2α) and inflammation (hsCRP, sCD40L, RANTES) were assessed.
Main Results:
- Clopidogrel significantly improved acetylcholine-induced vasodilation and L-NMMA responses, indicating enhanced NO bioavailability.
- No significant changes in vasodilation were observed in the placebo group.
- Urinary 8-iso-prostaglandin F2α and plasma hsCRP, sCD40L, and RANTES levels decreased with clopidogrel, but not placebo.
Conclusions:
- Clopidogrel improves endothelial NO bioavailability in symptomatic CAD patients.
- Adenosine diphosphate receptor blockade with clopidogrel reduces oxidative stress and inflammation.
- These findings suggest potential vasoprotective effects of clopidogrel beyond platelet aggregation inhibition.
Background:
Platelet stimulation and activation are known not only as prerequisite of clot formation but are increasingly recognized as important contributors to inflammation and vascular injury. The present study in patients with symptomatic coronary disease investigated whether platelet adenosine diphosphate receptor blockade by clopidogrel exerts beneficial effects on endothelial nitric oxide bioavailability, oxidative stress, and/or inflammatory status.
Methods And Results:
One hundred three consecutive patients with symptomatic coronary disease and long-term aspirin therapy were studied. Endothelium-dependent and -independent vasodilation was determined measuring forearm blood flow (FBF)-responses to acetylcholine with and without N(G)-monomethyl-L-arginin (L-NMMA) and sodium nitroprusside, by using venous occlusion plethysmography. Patients were randomized to receive additional treatment with clopidogrel or placebo. Vascular function tests were repeated after 5 weeks and showed significant improvement of acetylcholine-induced vasodilatation and L-NMMA responses in the clopidogrel-added group (max. FBF from 9.8+/-0.3 to 14.7+/-0.4; L-NMMA-response from 3.7+/-0.1 to 6.8+/-0.3 mL/100 mL/min). In contrast, no significant changes were observed in the placebo group. Sodium nitroprusside-induced vasodilation was not changed in either group. Urinary excretion of 8-iso-prostaglandin F2alpha and plasma levels of hsCRP, sCD40L, and RANTES were reduced in patients on additional treatment with clopidogrel, but not in patients on placebo.
Conclusions:
Clopidogrel improves endothelial nitric oxide bioavailability and diminishes biomarkers of oxidant stress and inflammation in patients with symptomatic coronary artery disease, suggesting that beyond inhibition of platelet aggregation, adenosine phosphate receptor blockade may also have promising vasoprotective effects.
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