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Aspirin and clopidogrel treatment impair nitric oxide biosynthesis by platelets.

Abstract：

:Aspirin and clopidogrel are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and beta-adrenoceptor (beta-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects (n=19) were randomized in a double-blind cross-over manner to receive aspirin or clopidogrel, each at 75 mg daily, for 14 days. Patients (n=17) of similar age with CHD, taking aspirin, were randomized double-blind to either continue on aspirin 75 mg daily or to receive clopidogrel 75 mg daily for 14 days. NO synthase (NOS) activity was measured from l-[(3)H]arginine to l-[(3)H]citrulline conversion, and cGMP was determined by radioimmunoassay, in platelets basally and following incubation with isoproterenol or albuterol (each at 10(-5) mol/L). In healthy subjects, aspirin did not affect basal NOS activity or cGMP in platelets, but suppressed the normal increase in both by isoproterenol and albuterol. Clopidogrel suppressed platelet NOS activity and cGMP both basally and in response to beta-AR agonists. In platelets from CHD patients, clopidogrel suppressed basal and beta-AR-stimulated NOS activity and cGMP as compared with aspirin. Platelet NOS activity and cGMP were lower in CHD subjects pre-randomization compared with healthy subjects both pre-randomization and post-aspirin. We conclude that chronic aspirin treatment suppresses beta-AR-stimulated but not basal platelet NO synthesis, as previously described, whereas chronic clopidogrel treatment suppresses both, with resultant functional consequences. Moreover, CHD may itself be associated with decreased platelet NO biosynthesis.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

O'Kane PD,Reebye V,Ji Y,Stratton P,Jackson G,Ferro A

doi

10.1016/j.yjmcc.2008.05.015

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

223-9

issue

2

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(08)00452-5

journal_volume

45

pub_type

杂志文章,随机对照试验

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