Angiotensin-(1-9) enhances stasis-induced venous thrombosis in the rat because of the impairment of fibrinolysis

J Renin Angiotensin Aldosterone Syst. 2014 Mar;15(1):13-21. doi: 10.1177/1470320313498631. Epub 2013 Jul 24.

Abstract

Introduction: ACE2 alternatively converts angiotensin (Ang) II into Ang-(1-7) and Ang I into Ang-(1-9). There is little information in the literature with respect to Ang-(1-9) properties. A number of studies show a link between peptides of the renin-angiotensin system and thrombosis.

Materials and methods: We have investigated the influence of Ang-(1-9) on stasis-induced venous thrombosis in the rat. The contribution of coagulation and fibrinolytic systems, angiotensin receptor type 1 (AT1) and MAS receptor in the mode of Ang-(1-9) action was also determined.

Results: Ang-(1-9) enhanced thrombosis development, decreased plasma concentration of tissue plasminogen activator and increased the level of its inhibitor (PAI-1). The action of Ang-(1-9) was reversed by selective antagonist of AT1 receptor, but not Ang-(1-7) antagonist. Ang-(1-9) did not bind to the AT1 receptor.

Conclusions: Ang-(1-9) enhances venous thrombosis in the rat because of the impairment of fibrinolysis. The prothrombotic effect of Ang-(1-9) is mediated by Ang II acting via the AT1 receptor.

Keywords: Thrombosis; angiotensin 1–9; angiotensins; fibrinolysis; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / metabolism
  • Angiotensin I / pharmacology*
  • Animals
  • Fibrinolysis / drug effects*
  • Male
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / physiology
  • Tissue Plasminogen Activator / metabolism
  • Venous Thrombosis / chemically induced*

Substances

  • Peptide Fragments
  • Plasminogen Activator Inhibitor 1
  • Receptor, Angiotensin, Type 1
  • angiotensin I (1-9)
  • Angiotensin I
  • Tissue Plasminogen Activator