title: Effects of selective cyclooxygenase isoform inhibition on systemic prostacyclin synthesis and on platelet function at rest and after exercise in healthy volunteers.
abstract: To test the hypothesis that selective inhibition of cyclooxygenase (COX)-2 would result in exercise-induced platelet activation by causing a shift in the endogenous thromboxane (TX)/prostacyclin balance, a double blind, randomized study comparing aspirin (300 mg/d) with rofecoxib (25 mg/d) (cross-over design, 14 days washout between treatments) in n = 10 trained healthy volunteers was carried out. Physical exercise resulted only in a minor platelet activation, as reflected by the expression of basal or ADP-stimulated platelet activation markers or basal plasma concentrations of TXB(2). Aspirin significantly reduced TXB(2) in plasma while rofecoxib significantly increased TXB(2) in urine. Although no increase in systemic prostacyclin concentration was observed, there was a significant exercise-related increase in both platelet cAMP and cGMP without any drug-related effects. It is concluded that, in trained healthy volunteers, selective inhibition of COX-1 (aspirin) or COX-2 (rofecoxib) does not affect systemic prostacyclin synthesis after physical exercise. However, our data do not exclude the possibility that in subjects at risk for atherothrombotic complications (e.g. patients with advanced atherosclerotic disease) COX-2 inhibitors may result in platelet activation by inhibiting endothelial prostacyclin formation.
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Germany. artur.weber@uk-essen.de
authors.forename: Artur-Aron
authors.initials: AA
authors.lastname: Weber
authors.forename: Hans-Karl
authors.initials: HK
authors.lastname: Heim
authors.forename: Marc
authors.initials: M
authors.lastname: Schumacher
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
authors.forename: Thomas
authors.initials: T
authors.lastname: Hohlfeld
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D050197:Atherosclerosis / Q000150:complications / Q000201:enzymology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004727:Endothelium / Q000201:enzymology; D011464:Epoprostenol / Q000097:blood; D015444:Exercise; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D012146:Rest; D012307:Risk Factors; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000201:enzymology / Q000209:etiology; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007527:Isoenzymes; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D001241:Aspirin