An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect
Clinics
;
66(5): 837-841, 2011. graf
Article
in English
| LILACS
| ID: lil-593849
ABSTRACT
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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Peptide Fragments
/
Angiotensin I
/
Venous Thrombosis
/
Fibrinolytic Agents
Limits:
Animals
Language:
English
Journal:
Clinics
Journal subject:
Medicine
Year:
2011
Type:
Article
Affiliation country:
Brazil
/
Germany
/
Mexico
Institution/Affiliation country:
Max-Delbrück Center for Molecular Medicine/DE
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