Angiotensin-(1–7) Modulates Angiotensin II-Induced Vasoconstriction in Human Mammary Artery

Purpose The renin-angiotensin system plays a key role in cardiovascular pathophysiology and one of its members, angiotensin-(1–7) (ANG-(1–7)), is now recognized as a peptide with the ability to counter-regulate angiotensin II (ANGII) effects. We sought to investigate ANG-(1–7) actions in human vessels, particularly its effect on ANGII-induced vasoconstriction in human mammary arteries (HMA). Methods Samples of HMA from patients submitted to coronary revascularization (22 patients, mean age 67 years) were cut into small rings, mounted in a myograph bath system, normalized and allowed to contract and dilate isometrically. In baseline experiments, the rings were incubated with ANG-(1–7) or vehicle, followed by increasing concentrations of ANGII. This protocol was repeated in the presence of A-779, PD123177, losartan and after mechanical endothelium removal. Western blot analysis and immunofluorescence were also performed in order to verify the presence of Mas receptor in HMA. Results ANG-(1–7) significantly attenuated ANGII-induced contraction, producing a maximal inhibition of approximately 65.2 %. This effect was not abolished by A-779, PD123177 or endothelium removal. In the presence of losartan, ANGII response was attenuated and no differences were observed between ANG-(1–7) and vehicle treated rings. Finally, we observed, for the first time, that the Mas receptor is expressed in HMA endothelium. Conclusions ANG-(1–7) significantly attenuates ANGII-induced vasoconstriction and, although the Mas receptor is expressed in HMA, this effect seems to be independent of its activation. Additionally, AT 2 receptor and endothelium are not involved in this mechanism, which suggests a direct effect on smooth muscle cells.