Angiotensin II Activates the Expression of Inflammatory Markers and the Migration of Inflammatory Cells into the Aorta of Normotensive Mice
Authors: Lima Rariane , Silva Juliane CS , Lima Cintia T , de Souza Leandro E , da Silva Maikon B , Baladi Marina G , Irigoyen Maria Claudia , Lacchini Silvia 
Published: June 2021

Introduction

Angiotensin II exerts important physiological functions on cardiovascular system homeostasis and may mediate actions leading to inflammatory responses. These actions lead to the activation of vascular smooth muscle cells (CMLVs) as well as the endothelium, in order to produce reactive oxygen species, inflammatory cytokines, chemokines and adhesion molecules inducing diapedesis of cells of myeloid origin. In this context, variations in Angiotensin II concentrations could occur in the body, leading to discrete increases that do not directly and immediately interfere with blood pressure but could stimulate the recruitment and activation of myeloid cells capable of initiating local inflammatory responses. Such a situation would provide important information for triggering a chronic process on the mechanisms of maintaining blood pressure and potentially leading to cardiovascular disease. This study aimed to verify the ability of angiotensin II to induce an inflammatory response in the aorta and if there is a relation with variations of arterial pressure, even if discrete.

Methods

For this, C57Bl/6 mice treated with saline solution (0.9%, control group) or Angiotensin II (30ng, Ang II group) were used. The animals were cannulated in the carotid artery and jugular vein, and 48 hours later PA and HR levels were recorded at baseline and after administration of saline or Ang II at 30 min, 1, 2, 6, 12 and 24 h. The evaluation of the baroreflex sensitivity was performed after administration of phenylephrine and sodium nitroprusside (100 and 150 ng). The evaluation of the inflammatory reaction in the aorta was performed by immunohistochemistry, using IL1‐β, TGF‐β, iNOS as inflammatory markers and CD45 as a marker of macrophages. The evaluation of α‐actin was performed in order to demonstrate a possible change in CMLV phenotype.

Results

At the end of the treatments, we verified that there was no change in blood pressure or heart rate. In addition, the treatment did not alter the baroreflex sensitivity. A biphasic response was observed both for IL1‐β and TGF‐β expression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and another more chronic increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (24 hours) in tunica adventitia. Immunoblotting to α‐actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic CMLV phenotype.

Conclusion

The results suggest that angiotensin II, even at doses that do not alter blood pressure, is capable of inducing the expression of inflammatory markers and the migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may be considered to be capable of increasing the propensity to develop a cardiovascular injury, even in normotensive individuals.

Support or Funding Information

This research was funded by Coordenação de Apoio a Pesquisa (CAPES) and São Paulo's state research funding agency Foundation (FAPESP).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.