An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect

Clinics (Sao Paulo). 2011;66(5):837-41. doi: 10.1590/s1807-59322011000500021.


Introduction and objective: The heptapeptide angiotensin-(1-7) is a component of the renin-angiotensin system, which promotes many beneficial cardiovascular effects, including antithrombotic activity. We have recently shown that the antithrombotic effect of angiotensin-(1-7) involves receptor Mas-mediated NO-release from platelets. Here, we describe an orally active formulation based on angiotensin-(1-7) inclusion in cyclodextrin [Ang-(1-7)- CyD] as an antithrombotic agent. Cyclodextrins are pharmaceutical tools that are used to enhance drug stability, absorption across biological barriers and gastric protection.

Method: To test the antithrombotic effect of Ang-(1-7)-CyD, thrombus formation was induced in the abdominal vena cava of spontaneously hypertensive rats that were pretreated either acutely or chronically with Ang-(1-7)-CyD. Male Mas-knockout and wild-type mice were used to verify the role of the Mas receptor on the effect of Ang-(1-7)-CyD.

Results: Acute or chronic oral treatment with Ang-(1-7)-CyD promoted an antithrombotic effect (measured by thrombus weight; all values are, respectively, untreated vs. treated animals) in spontaneously hypertensive rats (acute: 2.86 ± 0.43 mg vs. 1.14 ± 0.40 mg; chronic: 4.27 ± 1.03 mg vs. 1.39 ± 0.68 mg). This effect was abolished in Mas-knockout mice (thrombus weight in Mas wild-type: 0.76 ± 0.10 mg vs. 0.37 ± 0.02 mg; thrombus weight in Mas-knockout: 0.96 ± 0.11 mg vs. 0.87 ± 0.14 mg). Furthermore, the antithrombotic effect of Ang-(1-7)-CyD was associated with an increase in the plasma level of Angiotensin-(1-7).

Conclusion: These results show for the first time that the oral formulation Ang-(1-7)-CyD has biological activity and produces a Mas-dependent antithrombotic effect.

MeSH terms

  • Angiotensin I / therapeutic use*
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptide Fragments / therapeutic use*
  • Rats
  • Rats, Inbred SHR
  • Venous Thrombosis / drug therapy*


  • Fibrinolytic Agents
  • Peptide Fragments
  • Angiotensin I
  • angiotensin I (1-7)