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Angiotensin II constricts mouse iliac arteries: possible mechanism for aortic aneurysms

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Abstract

Abdominal aortic aneurysms (AAA) result from maladaptive remodeling of the vascular wall and reduces structural integrity. Angiotensin II (AngII) infusion has become a standard laboratory model for studying AAA initiation and progression. We determined the different vasoactive responses of various mouse arteries to Ang II. Ex vivo isometric tension analysis was conducted on 18-week-old male C57BL/6 mice (n = 4) brachiocephalic arteries (BC), iliac arteries (IL), and abdominal (AA) and thoracic aorta (TA). Arterial rings were mounted between organ hooks, gently stretched and an AngII dose response was performed. Rings were placed in 4% paraformaldehyde for immunohistochemistry analysis to quantify peptide expression of angiotensin type 1 (AT1R) and 2 receptors (AT2R) in the endothelium, media, and adventitia. Results from this study demonstrated vasoconstriction responses in IL were significantly higher at all AngII doses when compared to BC, and TA and AA responses (maximum constriction—IL: 68.64 ± 5.47% vs. BC: 1.96 ± 1.00%; TA: 3.13 ± 0.16% and AA: 2.75 ± 1.77%, p < 0.0001). Expression of AT1R was highest in the endothelium of IL (p < 0.05) and in the media and (p < 0.05) adventitia (p < 0.05) of AA. In contrast, AT2R expression was highest in endothelium (p < 0.05), media (p < 0.01, p < 0.05) and adventitia of TA. These results suggest that mouse arteries display different vasoactive responses to AngII, and the exaggerated response in IL arteries may play a role during AAA development.

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Acknowledgements

The authors would like to thank the Institute for Health and Sport, Victoria University for their support. L.K.G. and K.R.M. are recipients of Victoria University postgraduate scholarships.

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LKG, KRM, wrote the main manuscript text LKG, KRM, PK, MC, LG collected and analysed data RP, JD prepared figures PK, VA, AZ designed the study All authors reviewed the manuscript.

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Correspondence to Laura Kate Gadanec, Peter Kruzliak or Anthony Zulli.

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The authors declare no conflict of interest. Associate Professor Anthony Zulli co-owns Zultek Engineering, the provider of product OB8 used for isometric tension analysis.

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All experimental procedures were approved by the Ethics Committee of the Victoria University and were conducted in accordance with the regulations described in the Committee’s Guiding Principles Manual.

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Gadanec, L.K., McSweeney, K.R., Kubatka, P. et al. Angiotensin II constricts mouse iliac arteries: possible mechanism for aortic aneurysms. Mol Cell Biochem 479, 233–242 (2024). https://doi.org/10.1007/s11010-023-04724-0

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