Duration of inhibition of platelet prostaglandin formation and aggregation by ingested aspirin or indomethacin

Kocsis, James J.; Hernandovich, J.; Silver, Melvin J.; Smith, J B; Ingerman, Carol M.

doi:10.1016/0090-6980(73)90081-6

Cited by 128 publications

(35 citation statements)

References 4 publications

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“…O'Brien (10) initially suiggested that megakaryocytes were altered by aspirini because of a similar lag period in recovery of in vitro platelet aggregation after aspirin. Several other studies of aspirin's effect on platelets are conisistenit with the hvpothesis that megakarvocvte enzy me is inactivated (26)(27)(28). Alternative theories, suich as anl aspirin-senisitive nonexchangeable pool of nlew platelets in the spleen (29) would also explain a 2-day lag period; however, this seems to us to be a less likely possibility.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of platelet prostaglandin synthetase by oral aspirin.

Burch¹,

Stanford²,

Majerus³

1978

J. Clin. Invest.

533

194

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A B S T R A C T Aspirin inhibits platelet frinction by permanently acetylating the cyclooxygenase that forms prostaglandins. We determined the sensitivity of platelets to aspirin in normal subjects by measuring [3H-acetyl]aspirin-susceptible cyclooxygenase in washed platelets obtained at various times after aspirin ingestion. A single 325-mg aspirin dose inactivated 89% of platelet cyclooxygenase. The inhibition persisted for 2 days suggesting that oral aspirin also inactivated megakaryocyte cyclooxygenase. Thereafter, active enzyme returned with a time-course reflecting platelet turnover (life-span 8.2+2 days). Single doses of 20-650 mg aspirin resulted in 34->95% inhibition after 24 h. Daily doses of 20-325 mg aspirin for brief periods produced 61->95% inactivation when measured 24 h after cessation of the drug. Platelet cyclooxygenase is more sensitive to inactivation by aspirin than enzyme in sheep seminial vesicles.

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Section: Resultsmentioning

confidence: 99%

Inhibition of platelet prostaglandin synthetase by oral aspirin.

Burch¹,

Stanford²,

Majerus³

1978

J. Clin. Invest.

533

194

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“…Whether these metabolites are causally involved in the platelet release reaction is not yet resolved. Support for such a hypothesis comes from the observation that acetylsalicylic acid, a potent inhibitor of the platelet release reaction (9) and of prostaglandin synthesis (10,11), irreversibly inhibits cyclo-oxygenase (4, 12), the enzyme responsible for the conversion of arachidonic acid into endoperoxide prostaglandin G2, and also blocks the thrombin-induced burst in oxygen uptake (13) apparently necessary for the formation of these oxygenated products.…”

Section: Introductionmentioning

confidence: 99%

Vitamin E. An inhibitor of the platelet release reaction.

Steiner¹,

Anastasi²

1976

J. Clin. Invest.

207

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A B S T R A C T Formation of lipid peroxides rises sharply when platelets undergo the release reaction. In this study the in vitro effect of vitamin E on platelet aggregation was investigated. a-Tocopherol, an antioxidant of known inhibitory action on lipid peroxidation, was added to platelet suspensions in concentrations up to 1.5 mM. A dose-dependent reduction in platelet aggregation was observed, with complete inhibition of the secondary wave of aggregation at > 0.9 mM atocopherol. The inhibitory effect of a-tocopherol on the platelet release reaction was further documented by the decrease in aggregation-induced release of [14C]5-hydroxytryptamine from prelabeled platelets and by the reduction of N-acetylglucosaminidase activity released into the medium. The sharp rise in lipid peroxides normally associated with platelet aggregation was markedly reduced by a-tocopherol and also by acetylsalicylic acid, a known inhibitor of the platelet release reaction.In vivo studies examined the effect of oral vitamin E administration (1,200-2,400 IU daily) on plasma and platelet levels of a-tocopherol. Up to 1,800 IU daily, increasing dosages of vitamin E resulted in increasing concentrations of a-tocopherol in plasma and platelets, but intake of vitamin E in excess of this dosage failed to show any further increase in plasma or platelet levels.

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“…This treatment, while not affecting the general PG synthesis in the tissues at the time of blood sampling (see Hamberg, 1972), inhibits the release of PG from the platelets for 3-4 days after administration of the drug (Kocsis, Hernandovich, Silver, Smith & Ingerman, 1973).…”

Section: Analy8i8 Of Forearm Venous Prostaglandin E-like Substances (mentioning

confidence: 99%

Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.

Kilbom¹,

Wennmalm²

1976

The Journal of Physiology

191

108

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SUMMARY1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm.2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1.25 mg/kg body weight) was administered.3. Following 5 mmn of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Jndomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml

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Duration of inhibition of platelet prostaglandin formation and aggregation by ingested aspirin or indomethacin

Cited by 128 publications

References 4 publications

Inhibition of platelet prostaglandin synthetase by oral aspirin.

Inhibition of platelet prostaglandin synthetase by oral aspirin.

Vitamin E. An inhibitor of the platelet release reaction.

Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.

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