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Effects of a sustained thromboxane synthase inhibition on exercise‐induced changes in eicosanoid formation, catecholamine concentration, and platelet aggregation in humans
Author(s) -
Ohnishi Akihiro,
Ishizaki Takashi,
Echizen Hirotoshi,
Yasuda Kohtaro,
Fujiwara Hiroaki,
Tanaka Teruji
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.46
Subject(s) - chemistry , medicine , endocrinology , catecholamine , eicosanoid , platelet , epinephrine , eicosanoid metabolism , thromboxane a synthase , thromboxane a2 , thromboxane b2 , sympathoadrenal system , thromboxane , platelet activation , biochemistry , arachidonic acid , enzyme
In an effort to characterize an interaction between the eicosanoids and sympathoadrenal system on platelet aggregation, we tried to determine if a sustained thromboxane A 2 (TXA 2 ) synthase inhibition would modulate changes in eicosanoid formation, catecholamine concentration, and platelet aggregation induced by a physical stress. We measured thromboxane B 2 (TXB 2 ), ll‐dehydro‐TXB 2 , 6‐ketoprostaglandin F 1α (6‐keto‐PGF 1α ), norepinephrine, and epinephrine in vivo and platelet aggregation ex vivo before and after a treadmill exercise with and without the oral doses (400 mg twice daily for 7 days) of a new selective TXA 2 synthase inhibitor (DP‐1904) in nine healthy male subjects. The exercise tests performed on the pretreatment day (day 0) and posttreatment day (day 7) gave a similar result. DP‐1904 caused a decrease in serum and urinary TXB 2 and urinary ll‐dehydro‐TXB 2 ( p < 0.001 to p < 0.01) and an increase in serum 6‐keto‐PGF 1α ( p < 0.001 to p < 0.05) throughout the dosing interval on days 4 and 7. Despite the drug effect on eicosanoid formation at rest and after exercise, the exercise‐induced plasma norepinephrine and epinephrine concentrations did not differ between days 0 and 7. The 7‐day treatment decreased ( p < 0.01) platelet aggregation induced both by adenosine diphosphate and by collagen at rest. However, the exercise increased ( p < 0.01) platelet aggregation by the two aggregators, resulting in the disappearance of the drug‐induced antiaggregatory effects observed at rest. The treatment with a TXA 2 synthase inhibitor does not appear to attain the antithrombotic action during an exercise despite the occurrence of a sustained endoperoxide shunting. Clinical Pharmacology and Therapeutics (1992) 51, 454–464; doi: 10.1038/clpt.1992.46