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The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets

Item Type:Article
Title:The antithrombotic effect of angiotensin-(1-7) involves mas-mediated NO release from platelets
Creators Name:Fraga-Silva, R.A. and Pinheiro, S.V. and Goncalves, A.C. and Alenina, N. and Bader, M. and Santos, R.A.
Abstract:The antithrombotic effect of angiotensin(Ang)-(1-7) has been reported, but the mechanism of this effect is not known. We investigated the participation of platelets and receptor Mas-related mechanisms in this action. We used Western blotting to test for the presence of Mas protein in rat platelets and used fluorescent-labeled FAM-Ang-(1-7) to determine the specific binding for Ang-(1-7) and its displacement by the receptor Mas antagonist A-779 in rat platelets and in Mas(-/ -) and Mas(+/+) mice platelets. To test whether Ang-(1-7) induces NO release from platelets, we used the NO indicator DAF-FM. In addition we examined the role of Mas in the Ang-(1-7) antithrombotic effect on induced thrombi in the vena cava of male Mas(-/ -) and Mas(+/+) mice. The functional relevance of Mas in hemostasis was evaluated by determining bleeding time in Mas(+/+) and Mas(-/ -) mice. We observed the presence of Mas protein in platelets, as indicated by Western Blot, and displacement of the binding of fluorescent Ang-(1-7) to rat platelets by A-779. Furthermore, in Mas(+/+) mouse platelets we found specific binding for Ang-(1-7), which was absent in Mas(-/ -) mouse platelets. Ang-(1-7) released NO from rat and Mas(+/+) mouse platelets, and A-779 blocked this effect. The NO release stimulated by Ang-(1-7) was abolished in Mas(-/ -) mouse platelets. Ang-(1-7) inhibited thrombus formation in Mas(+/+) mice. Strikingly, this effect was abolished in Mas(-) (/) (-)mice. Moreover, Mas deficiency resulted in a significant decrease in bleeding time (8.50 +/- 1.47 vs. 4.28 +/- 0.66 min). This study is the first to show the presence of Mas protein and specific binding for Ang-(1-7) in rat and mouse platelets. Our data also suggest that the Ang-(1-7) antithrombotic effect involves Mas-mediated NO release from platelets. More importantly, we showed that the antithrombotic effect of Ang-(1-7) in vivo is Mas dependent and that Mas is functionally important in hemostasis.
Keywords:Angiotensin I, Angiotensin II, Bleeding Time, Blood Coagulation, Blood Platelets, Nitric Oxide, Peptide Fragments, Proto-Oncogene Proteins, G-Protein-Coupled Receptors, Vasoconstrictor Agents, Vasodilator Agents, Animals, Mice, Rats
Source:Molecular Medicine
Publisher:Blackwell Publishing
Page Range:28-35
Date:January 2008
Official Publication:https://doi.org/10.2119/2007-00073.Fraga-Silva
PubMed:View item in PubMed

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