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Vasoconstriction with thromboxane A2 induces ulceration of the gastric mucosa

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Abstract

Thromboxane A2 (TXA2) is formed from the fatty acid precursor, arachidonic acid (AA), by the sequential actions of the enzymes cyclooxygenase and thromboxane synthetase1. It is readily generated by platelets and is a potent vasoconstrictor and inducer of platelet aggregation1,2. Studies in dogs show that the addition of AA to blood flowing through an incubation coil leads to production of TXA2, characterized by its instability and its ability to contract isolated strips of vascular tissue3. We now report that the formation of TXA2 from AA in blood can be inhibited by 1-benzylimidazole, a thromboxane synthetase inhibitor, and selectively by very low doses of indomethacin. In conditions of TXA2 inhibition, a vasodilator AA metabolite, presumably prostacyclin, is formed in the stomach. We show that TXA2 is a powerful gastric vasoconstrictor and can extensively damage the gastric mucosa, and suggest that it may be involved in the pathogenesis of certain ulcerative disorders of the stomach.

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Authors and Affiliations

  1. Department of Prostaglandin Research, Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, UK

    B. J. R. Whittle, G. L. Kauffman & S. Moncada

Authors
  1. B. J. R. Whittle
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  2. G. L. Kauffman
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  3. S. Moncada
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Whittle, B., Kauffman, G. & Moncada, S. Vasoconstriction with thromboxane A2 induces ulceration of the gastric mucosa. Nature 292, 472–474 (1981). https://doi.org/10.1038/292472a0

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