Angiotensin (1-7)-attenuated vasoconstriction is associated with the Interleukin-10 signaling pathway

Angiotensin-1-7 [Ang-(1-7)] is an essential peptide of the renin-angiotensin system that promotes benefits modulating effects in different tissues. Similarly, interleukin-10 (IL-10) exhibits an immunomodulatory action on the vasculature. This study aimed to evaluate whether Ang-(1-7) levels attenuates vascular contractile response, mediated by IL-10-pathway (JAK1/STAT3/IL-10).

Aortas from male mice C57BL/6J and knockout for IL-10 (IL-10^-/-) were incubated with Ang-(1-7) [10 μM] or vehicle, during 5 min, 1 h, 6 h, 12 h, and 24 h. Concentration-response curves to phenylephrine, western blotting, and flow cytometry analysis was performed to evaluate the contractile response, protein expression, and IL-10 levels, respectively.

Incubation with Ang-(1-7) produced a time-dependent increase in Janus kinases 1 (JAK1) expression, as well as increased expression and activity of the signal transducer and activator of transcription 3 (STAT3) protein. However, this effect was not observed in knockout animals for IL-10. After 12 h of Ang-(1-7) treatment, arteries from control mice displayed decreased vascular reactivity to phenylephrine, but this effect was not observed in the absence of endogenous IL-10. Additionally, incubation with Ang-(1-7) augments IL-10 levels after 6 h, 12 h, and 24 h of incubation.

These results demonstrated the role of Ang-(1-7) in the IL-10 signaling pathway and its effects in the vascular contractility response. Thus, these findings suggest a new synergic action where Ang-(1-7) and IL-10 converge into a protective mechanism against vascular dysfunction.