Involvement of superoxide anion and platelet-activating factor in increased tissue-type plasminogen activator during rat gastric microvascular damages

I. Kurose, M. Suematsu, S. Miura, M. Suzuki, H. Nagata, T. Morishita, E. Sekizuka, M. Tsuchiya

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The role of tissue-type plasminogen activator (t-PA) was investigated in the gastric ulcer formation induced by microvascular derangement. The rat stomach was exposed and repeated electrical stimuli (irritation) were applied on the small arterial wall close to the lesser curvature to induce mucosal ischemia followed by hyperemia. The t-PA activity in the regional blood of the stomach was significantly elevated as early as 5min after the irritation. Immunohistochemical study using anti-t-PA monoclonal antibody revealed that t-PA was detectable in the endothelial cells of capillaries and collecting venules, suggesting the involvement of endothelium-mediated fibrinolytic activity in the irritation-induced ulcer formation. Pretreatment of SOD or allopurinol significantly attenuated the irritation-induced t-PA activation, suggesting that the t-PA activity was modulated by xanthine oxidase-associated superoxide anions. CV-6209, a selective antagonist of platelet-activating factor (PAF), also prevented the activation of t-PA as well as ulcer formation, providing a concept that PAF may be associated with the local fibrinolytic activation which may cause hemorrhagic changes in the gastric mucosal microvasculature. The present study supports the hypothesis that increased t-PA activity may reflect the microvascular endothelial damages caused by vasomotor derangement and suggests that oxygen-derived free radicals may participate in the regulation of endothelium-derived fibrinolytic activities in the mucosal microvasculature.

Original languageEnglish
Pages (from-to)241-248
Number of pages8
JournalThrombosis Research
Volume62
Issue number4
DOIs
Publication statusPublished - 1991 May 15

Keywords

  • free radicals
  • gastric ulcer
  • microcirculation
  • platelet-activating factor
  • tissue-type plasminogen activator

ASJC Scopus subject areas

  • Hematology

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