Vasodilator Effect of Angiotensin-(1-7) on Vascular Coronary Bed of Rats: Role of Mas, ACE and ACE2

Author(s): Patricia Lanza de Moraes, Lucas M. Kangussu, Carlos Henrique Castro, Alvair P. Almeida, Robson A.S. Santos, Anderson J. Ferreira*.

Journal Name: Protein & Peptide Letters

Volume 24 , Issue 9 , 2017

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Abstract:

Background: Angiotensin(Ang)-(1-7) is a biologically active member of the reninangiotensin system that participates of the regulation of blood pressure. Although Ang-(1-7) is able to potentiate the vasodilator effect of bradykinin in coronary bed of rats, a direct vasodilator effect of Ang-(1-7) in this vascular bed has not been characterized.

Objectives: The aim of this study was to evaluate the mechanisms involved in the vasodilator effect of Ang-(1-7) in the vasculature of isolated rat hearts perfused according to the Langendorff technique at constant flow.

Methods: Isolated hearts, after approximately 30 minutes of stabilization, were perfused with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1-7). The participation of the Ang-(1-7) receptor Mas, AT1 receptor, angiotensin-converting enzyme (ACE) and ACE2 was evaluated perfusing hearts with a combination of Ang-(1-7) plus A779, Ang-(1-7) plus losartan, Ang-(1-7) plus captopril/enalapril and Ang-(1-7) plus DX-600, respectively.

Results: Ang-(1-7) induced a significant decrease in the perfusion pressure, indicating a direct vasodilatation action of this peptide in the coronary bed. This effect was abolished by A779, captopril, enalapril and DX-600 an ACE2-specific inhibitor. However, AT1 blockade did not blunt the Ang-(1-7) effect. No significant changes were observed in heart rate, as well as in contractile tension and ±dT/dt. Moreover, immunohistochemical analysis showed the presence of Ang-(1-7) and Mas in coronary vessels.

Conclusion: The Ang-(1-7) concentration used in this study was unable to induce changes in the cardiac function since no consistent alterations in contraction force and HR were viewed after Ang- (1-7) perfusion. In summary, this study showed that Ang-(1-7) induces vasodilation in the coronary bed of rats and this effect involves coupling to Mas receptor and interaction with ACE and ACE2.

Keywords: Angiotensin-(1-7), Mas receptor, Angiotensin-converting enzyme 2, heart, A779, AT1 receptor, Langendorff technique.

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Article Details

VOLUME: 24
ISSUE: 9
Year: 2017
Page: [869 - 875]
Pages: 7
DOI: 10.2174/0929866524666170728154459
Price: $58

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