PhD Scientific Days 2022

Translational Medicine III.

Effect of Chronic Angiotensin Administration on C3a-induced Vasoconstriction in Mice

Text of the abstract

Introduction: Our workgroup has previously located the C3a receptor (C3aR) in multiple cell types of the mouse arterial wall and found that the vasoconstrictor effect of C3a could be mediated by the resident macrophages in the adventitia through releasing thromboxane A2.

Aims: The objective of this study was to determine the effects of systemic inflammation provoked by chronic angiotensin II (Ang II) administration on C3a-induced vasoconstriction in mice.

Methods: Thoracic and abdominal aortic segments of adult male C57/Bl6 mice were isolated and the changes in the isometric tension of the vascular segments were measured using myography. The mice were randomly assigned to two groups and received either infusion with Ang II (520 ng/kg/min) or saline for 14 days by using micro-osmotic pumps implanted in the subscapular region. The expression of C3aR and the mouse macrophage marker F4/80 were determined with conventional qPCR. To examine the mechanism of the contraction the cyclooxygenase inhibitor indomethacin and SQ29548, a thromboxane receptor antagonist, were used.

Results: Ang II treatment increased the expression of C3aR in the vascular segments. These vessels showed an increased response to C3a (63–77) compared to controls that received saline infusion. Our qPCR revealed that the Ang II infusion increased the expression of F4/80 and C3aR in the aortas, especially in the adventitia. After the removal of the endothelium the vasoconstriction increased, whereas the administration of COX and TP receptor inhibitors and the removal of the adventitia made the vessels unresponsive to C3a.

Conclusion: These results indicate that the administration of Ang II leads to an increased vasoconstrictor response to C3a and an increased expression of C3aR in the aortic wall. By the detachment of the adventitia the vasoconstriction was abolished. In conclusion, our findings suggest that the C3a-induced vasoconstriction of the mouse aorta is mediated by macrophages accumulated in the adventitia.

Funding: NKFIH K-125174, K-135683, K-139230, 2020-1.1.6-JÖVŐ-2021-00010, EFOP-3.6.3-VEKOP-16-2017-00009, TKP2021-EGA-25.