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Interleukin 17A infusion has no acute or long-term hypertensive action in conscious unrestrained male mice

  • Integrative physiology
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Abstract

Interleukin 17A (IL-17A) is a candidate mediator of inflammation-driven hypertension, but its direct effect on blood pressure is obscure. The present study was designed to test the hypothesis that systemic IL-17A concentration-dependently increases blood pressure and amplifies ANGII-induced hypertension in mice. Blood pressure was measured by indwelling chronic femoral catheters before and during IL-17A infusion w/wo angiotensin II (ANGII, 60ng/kg/min) in male FVB/n mice. Baseline blood pressure was recorded, and three experimental series were conducted: (1) IL-17A infusion with increasing concentrations over 6 days (two series with IL-17A from two vendors, n = 11); (2) ANGII infusion with IL-17A or vehicle for 9 days (n = 11); and (3) acute bolus infusions with four different concentrations (n = 5). Plasma IL-17A and IL-6 concentrations were determined by ELISA. Mean arterial and systolic blood pressures (MAP, SBP) decreased significantly after IL-17A infusion while heart rate was unchanged. In these mice, plasma IL-17A and IL-6 concentrations increased up to 3500- and 2.4-fold, respectively, above baseline. ANGII infusion increased MAP (~ 25 mmHg) and co-infusion of IL-17A attenuated ANGII-induced hypertension by 4.0 mmHg. Here, plasma IL-17A increased 350-fold above baseline. Acute IL-17A bolus infusion did not change blood pressure or heart rate. IL-17A receptor and IL-6 mRNAs were detected in aorta, heart, and kidneys of mice after IL-17A infusion. Nonphysiologically high concentrations of IL-17A reduce baseline blood pressure and increase IL-6 formation in male FVB/n mice. It is concluded that IL-17A is less likely to drive hypertension as the sole cytokine mediator during inflammation in vivo.

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Acknowledgements

We thank laboratory technician Jesper Kingo Andresen for excellent assistance with measuring plasma IL-17A and IL-6.

Funding

The study was supported by the A.P. Møller Foundation, The Novo Nordisk Foundation, Independent Research Fund Denmark, Karen Elise Jensen Foundation, and Augustinus Foundation.

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Authors and Affiliations

  1. Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Sai Sindhu Thangaraj, Camilla Enggaard, Jane Stubbe, Pernille B. L. Hansen, Per Svenningsen & Boye L. Jensen

  2. Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Yaseelan Palarasah

  3. Bioscience Renal, Research and early development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

    Pernille B. L. Hansen

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  1. Sai Sindhu Thangaraj
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Contributions

BLJ and SST conceived the idea and designed the animal experiments; SST and CE conducted animal and laboratory experiments and analyzed the data; SST, BLJ, JS, PS, YP, and PBLH interpreted results and experiments; SST prepared figures; SST and BLJ have drafted the manuscript. All the authors revised the manuscript and approved for final submission.

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Correspondence to Boye L. Jensen.

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The authors declare no conflicts of interest. PBL Hansen is an employee and shareholder at AstraZeneca.

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Thangaraj, S.S., Enggaard, C., Stubbe, J. et al. Interleukin 17A infusion has no acute or long-term hypertensive action in conscious unrestrained male mice. Pflugers Arch - Eur J Physiol 474, 709–719 (2022). https://doi.org/10.1007/s00424-022-02705-8

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