Differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation.

Clopidogrel plus aspirin is a standard antiplatelet aggregation regimen in cardiovascular diseases, especially after implantation of a coronary stent. Interaction between clopidogrel and proton pump inhibitors theoretically reduces clopidogrel's antiaggregation effect, but the evidence is controversial. A total of 30 healthy subjects and 74 patients with a coronary stent were given a 300 mg loading dose of aspirin and 300 mg clopidogrel and then 100 mg aspirin/75 mg clopidogrel daily for 14 days. Subgroups were concomitantly treated or not treated with esomeprazole (20 mg/day). Clopidogrel significantly reduced adenosine diphosphate-induced platelet aggregation in healthy and stent-implanted subjects on days 7 and 14. Healthy subjects receiving esomeprazole showed a significantly higher platelet aggregation rate than those not receiving esomeprazole, but esomeprazole had no effect in patients with a stent. Aspirin plus clopidogrel did not result in significant gastrointestinal complications. These differential effects of esomeprazole on the antiplatelet activity of clopidogrel in healthy individuals and patients after coronary stent implantation merit further investigation.

Farnesoid X receptor regulates vascular reactivity through nitric oxide mechanism.

Farnesoid X receptor (FXR), a ligand-activated transcription factor and a member of nuclear receptor family, is not only highly expressed in the adrenal cortex, intestine, kidney and liver, but also has recently been found in the vasculature. However, the evidence on the roles of FXR in the vasculature is limited and whether FXR regulates vascular reactivity is poorly understood. In present study, we investigated the expression of FXR protein in rat vasculature by immunohistochemical method and tested the effects of FXR activation by chenodeoxycholic acid (CDCA) on thoracic aortic contraction and dilation. We also detected the level of nitrite/nitrate (NOx) and superoxide in the thoracic aortic segments. We found that FXR was expressed in rat carotid arteries, thoracic aorta, abdominal aorta and femoral arteries. FXR activation by CDCA significantly (P<0.01) inhibited the contractile responses of rat thoracic aorta rings to KCl and phenylephrine. The cumulative concentrations of CDCA caused a concentration-dependent relaxation, which could be partly impaired by L-NAME, an inhibitor of nitric oxide (NO) synthase. The NOx content in thoracic aorta significantly (P<0.01) increased when treated with CDCA. Meanwhile, the vascular redox status was not altered by high concentration of CDCA. The present study suggested that FXR regulated vascular reactivity through NO mechanism, which merits further attention.