Long-term inhibition of nitric oxide synthesis increases arterial thrombogenecity in rat carotid artery

Mayuko Kubo-Inoue, Kensuke Egashira, Makoto Usui, Masao Takemoto, Kisho Ohtani, Makoto Katoh, Hiroaki Shimokawa, Akira Takeshita

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35 Citations (Scopus)

Abstract

Reduced activity of endothelial nitric oxide (NO) may be involved in thrombus formation on atherosclerotic plaques, a major cause of acute coronary syndrome. However, mechanisms of such increase in arterial thrombogenecity have not been fully understood. We previously reported that long-term inhibition of NO synthesis by administration of NG-nitro-L-arginine methyl ester (L-NAME) causes hypertension and activates vascular tissue angiotensin-converting enzyme (ACE) activity. We used this model to investigate the mechanism by which long-term impairment of NO activity increases arterial thrombogenecity. We observed cyclic flow variations (CFVs), a reliable marker of platelet thrombi, after the production of stenosis of the carotid artery in rats treated with L-NAME for 4 wk. The thrombin antagonist argatroban suppressed the CFVs. The CFVs were detected in rats receiving L-NAME plus hydralazine but not in rats receiving L-NAME plus an ACE inhibitor (imidapril). Treatment with the ACE inhibitor imidapril, but not with hydralazine, prevented L-NAME-induced increases in carotid arterial ACE activity and attenuated tissue factor expression. These results suggest that long-term inhibition of endothelial NO synthesis may increase arterial thrombogenecity at least in part through angiotensin II-induced induction of tissue factor and the resultant thrombin generation. These data provide a new insight as to how endothelial NO exhibits antithrombogenic properties of the endothelium.

Original languageEnglish
Pages (from-to)H1478-H1484
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number4 51-4
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • Angiotensin-converting enzyme
  • Thrombin
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Kubo-Inoue, M., Egashira, K., Usui, M., Takemoto, M., Ohtani, K., Katoh, M., Shimokawa, H., & Takeshita, A. (2002). Long-term inhibition of nitric oxide synthesis increases arterial thrombogenecity in rat carotid artery. American Journal of Physiology - Heart and Circulatory Physiology, 282(4 51-4), H1478-H1484. https://doi.org/10.1152/ajpheart.00739.2001