Download PDF
Thromb Haemost 1980; 44(01): 016-022
DOI: 10.1055/s-0038-1650072
Original Article
Schattauer GmbH Stuttgart

Thromboxane Generation in Patients with Essential Hypertension or Cerebrovascular Disease and Effect of Oral Aspirin

M Matsumoto
*   The First Department of Internal Medicine, Osaka University Medical School, Osaka, Japan
,
T Nukada
*   The First Department of Internal Medicine, Osaka University Medical School, Osaka, Japan
,
O Uyama
*   The First Department of Internal Medicine, Osaka University Medical School, Osaka, Japan
,
S Yoneda
*   The First Department of Internal Medicine, Osaka University Medical School, Osaka, Japan
,
M Imaizumi
*   The First Department of Internal Medicine, Osaka University Medical School, Osaka, Japan
,
T Miyamoto
**   The Central Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan
,
N Kayama
**   The Central Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan
› Author Affiliations
Further Information

Publication History

Received 24 March 1980

Accepted 11 June 1980

Publication Date:
13 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

The ability of platelets to synthesize thromboxane B2 (TxB2) from arachidonic acid (AA) or prostaglandin H2 (PGH2) was studied in 26 control subjects, 40 patients with essential hypertension, 20 patients with cerebrovascular disease (CVD) not taking aspirin and 11 patients with CVD taking aspirin. The activity of platelets to form TxB2 from AA or PGH2 was measured using 1 — 14C arachidonic acid or 1—14C PGH2 as a substrate. There was no significant difference in TxB2 generation from AA or PGH2 among the platelets collected from the control subjects, hypertensive patients and CVD patients not taking aspirin.

In CVD patients taking aspirin, marked suppression was observed in TxB2 synthesis from AA, but no suppression in TxB2 synthesis from PGH2. At least 750 mg aspirin per day were required for nearly complete suppression of TxB2 generation from AA.

Key words

Thromboxane generation - Hypertension - Cerebrovascular disease - Aspirin - Prostaglandin - Platelet
 

  • References

  • 1 Hamberg M, Svensson J, Samuelsson B. Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Nat Acad Sci USA 1975; 72: 2994-2998
    CrossrefPubMedGoogle Scholar
  • 2 Blackwell GJ, Duncombe WG, Flower RJ, Parsons MF, Vane JR. The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs. Br J Pharmacol 1977; 59: 353-366
    CrossrefPubMedGoogle Scholar
  • 3 Bunting S, Moncada S, Vane JR. The effects of prostaglandin endoperoxides and thromboxane A2 on strips of rabbit coeliac artery and certain other smooth muscle preparations. Br J Pharmacol 1976; 57: 462p-463p
    PubMedGoogle Scholar
  • 4 Moncada S, Gryglewski RJ, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelets aggregation. Nature 1976; 263: 663-665
    CrossrefPubMedGoogle Scholar
  • 5 Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 1976; 12: 685-713
    CrossrefPubMedGoogle Scholar
  • 6 Moncada S, Gryglewski RJ, Bunting S, Vane JR. A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 1976; 12: 715-737
    CrossrefPubMedGoogle Scholar
  • 7 Gryglewski RJ, Dembińska-Kièć A, Zmuda A, Gryglewska T. Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries and platelets at various stages of experimental atherosclerosis in rabbits. Atherosclerosis 1978; 31: 385-394
    CrossrefPubMedGoogle Scholar
  • 8 Szczeklik A, Gryglewski RJ, Musiał J, Grodzińska L, Serwońska M, Marcinkiewicz E. Thromboxane generation and platelet aggregation in survivals of myocardial infarction. Thromb. Haemostas 1978; 40: 66-74
    PubMedGoogle Scholar
  • 9 Sinzinger H, Feigl W, Silberbauer K. Prostacyclin generation in atherosclerotic arteries. Lancet 1979; 2: 469
    PubMedGoogle Scholar
  • 10 Sinzinger H, Clopath P, Silberbauer K, Auerswald W. Prostacyclin synthesis in human and experimental atherosclerosis. Atherosclerosis 1979; 34: 345-347
    CrossrefPubMedGoogle Scholar
  • 11 Dembińska-Kièć A, Rücker W, Schönhöfer PS. Prostacyclin-dependent differences in TXA2 formation by platelets from normal and atherosclerotic rabbits. Atherosclerosis 1979; 33: 217-226
    CrossrefPubMedGoogle Scholar
  • 12 Amezcua JL, O'Grady J, Salmon JA, Moncada S. Prolonged paradoxical effect of aspirin on platelet behaviour and bleeding time in man. Thromb Res 1979; 16: 69-79
    CrossrefPubMedGoogle Scholar
  • 13 Pace-Asciak CR, Carrara MC, Rangaraj G, Nicolaou KC. Enhanced formation of PGI2, a potent hypotensive substance, by aortic rings and homogenates of the spontaneously hypertensive rat. Prostaglandins, 1978; 15: 1005-1012
    CrossrefPubMedGoogle Scholar
  • 14 Okuma M, Yamori Y, Ohta K, Uchino H. Production of prostacyclin-like substance in stroke-prone and stroke-resistant spontaneously hypertensive rats. Prostaglandins, 1979; 17: 1-7
    CrossrefPubMedGoogle Scholar
  • 15 Yoshimoto T, Yamamoto S, Hayaishi O. Selective inhibition of prostaglandin endoperoxide thromboxane isomerase by 1-carboxyalkylimidazoles. Prostaglandins 1978; 16: 529-540
    CrossrefPubMedGoogle Scholar
  • 16 Miyamoto T, Yamamoto S, Hayaishi O. Prostaglandin synthetase system – Resolution into oxygenase and isomerase components. Pro Nat Acad Sci USA 1974; 71: 3645-3648
    CrossrefPubMedGoogle Scholar
  • 17 Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 1973; 19: 1350-1356
    PubMedGoogle Scholar
  • 18 Eggstein M, Kreutz FH. Eine neue Bestimmung der Neutralfette im Blutserum und Gewebe. I. Mitteilung. Prinzip, Durchführung und Besprechung der Methode. Klin Wochenschr 1966; 44: 262-267
    CrossrefPubMedGoogle Scholar
  • 19 Danta G. Platelet adhesiveness in cerebrovascular disease. Atherosclerosis 1970; 11: 223-233
    CrossrefPubMedGoogle Scholar
  • 20 Andersen LA, Gormsen J. Platelet aggregation and fibrinolytic activity in transient cerebral ischemia. Acta Neurol Scand 1976; 55: 76-82
    PubMedGoogle Scholar
  • 21 Couch JR, Hassanein RS. Platelet aggregation, stroke, and transient ischemic attack in middle-aged and elderly patients. Neurology 1976; 26: 888-895
    CrossrefPubMedGoogle Scholar
  • 22 Kobayashi I, Fujita T, Yamazaki H. Platelet aggregability measured by screen filtration pressure method in cerebrovascular diseases. Stroke 1976; 7: 406-409
    CrossrefPubMedGoogle Scholar
  • 23 Dougherty Jr JH, Levy DE, Weksler BB. Platelet activation in acute cerebral ischemia. Lancet 1977; 1: 821-824
    PubMedGoogle Scholar
  • 24 Mehta J, Mehta P, Burger C, Pepine CJ. Platelet aggregation studies in coronary artery disease. Part 4. Effect of aspirin. Atherosclerosis 1978; 31: 169-175
    CrossrefPubMedGoogle Scholar
  • 25 Matsumoto M, Nukada T, Uyama O, Yoneda S, Imaizumi M, Miyamoto T, Kayama N. Arachidonic acid induced platelet aggregation in patients with essential hypertension and cerebrovascular disease. (in preparation)
    PubMedGoogle Scholar
  • 26 Hamberg M, Samuelsson B. Prostaglandin endoperoxides. Novel transformation of arachidonic acid in human platelets. Proc Nat Acad Sci USA 1974; 71: 3400-3404
    CrossrefPubMedGoogle Scholar
  • 27 Nugteren DH. Arachidonate lipoxygenase in blood platelets. Biochim Biophys Acta 1975; 380: 299-307
    CrossrefPubMedGoogle Scholar
  • 28 O'Brien JR, Oxon DM, Path FC. Effects of salicylates on human platelets. Lancet 1968; 1: 779-783
    PubMedGoogle Scholar
  • 29 Rowland M, Riegelman S, Harris PA, Sholkoff SD. Absorption kinetics of aspirin in man following oral administration of an aqueous solution. J Pharm Sci 1972; 61: 379-385
    CrossrefPubMedGoogle Scholar
  • 30 Woodbury DM, Fingl E. Analgesic-antipyretics, anti-inflammatory agents, and drugs employed in the therapy of gout. In: Goodman LS, Gilman A. The Pharmacological Basis of Therapeutics . Macmillan Publishing Co., New York: 1975. p. 325-358
    Google Scholar
  • 31 Rance MJ, Jordan GJ, Nichols JD. A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography. J Pharm and Pharmacol 1975; 27: 425-429
    CrossrefPubMedGoogle Scholar
  • 32 Burch JW, Stanford N, Majerus PW. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest 1978; 61: 314-319
    CrossrefPubMedGoogle Scholar
  • 33 Szczeklik A, Gryglewski RJ, Grodzińska L, Musiał J, Serwońska M, Marcinkiewicz E. Platelet aggregability, thromboxane A2 and malonaldehyde formation following administration of aspirin to man. Thromb Res 1979; 15: 405-413
    CrossrefPubMedGoogle Scholar
  • 34 Dyken ML. Assessment of the role of antiplatelet aggregating agents in transient ischemic attacks, stroke and death. Stroke 1979; 10: 602-604
    PubMedGoogle Scholar