Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.

Oliveira, T. C. d. S.; Viegas, K. A. d. S.; Lima, R. S. d.; Campos, L. C. G.; Barauna, V. G.; Curi, R.; Irigoyen, M. C.; Lacchini, S.

doi:10.1101/2023.11.06.563831

bioRxiv · 10.1101/2023.11.06.563831

Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.

Oliveira, T. C. d. S.·Viegas, K. A. d. S.·Lima, R. S. d.·Campos, L. C. G.·Barauna, V. G.·Curi, R.·Irigoyen, M. C.·Lacchini, S.

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Abstract

To verify if a low dose of angiotensin II (Ang II) can induce an inflammatory response in cardiac arteries, even though blood pressure remains at normal values. Were used C57Bl/6J male mice treated with a low dose of Ang II (30ng/kg IP) and AT1R blockers. Blood pressure was recorded after 10, 30, 60min, 2 and 6hours after Saline or Ang II injection. Time curve (30 and 60min, 2, 6, 12, 24, and 48hours after treatment) for expression of inflammatory markers was evaluated in cardiac arteries (TGF-{beta}, IL-1{beta}, IL-6, TNF- and ICAM-1) by immunohistochemistry and western blot. Serum TNF- and IL-6 were analyzed by ELISA. Although Ang II did not alter blood pressure, local TGF- and IL-6 presented an early increase in cardiac arteries. IL-1{beta} and ICAM-1 participated in a late response to Ang II (12 hours). Ang II group showed a systemic increase of IL-6 30 to 60 minutes after treatment. AT1 and AT2 receptor blockers (losartan, 20mg/kg, and PD123.319, 15mg/kg) were given alone or concomitant to Ang II. This combination showed that Ang II increases TGF-{beta} and IL-6 by acting on the AT1 receptor in a fast response. IL-1{beta} regulation by Ang II seems to be mediated by both AT1 and AT2 receptors. The results suggest that, independently of hemodynamic influences, Ang II, acting on AT1R, leads to the expression of inflammatory markers in cardiac vessels. AT2 receptor seems to be involved in the counterbalance of AT1R during modulation of IL-1{beta} production in cardiac arteries.

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Oliveira, T. C. d. S., Viegas, K. A. d. S., Lima, R. S. d., Campos, L. C. G., Barauna, V. G., Curi, R., Irigoyen, M. C., Lacchini, S.. 2023-11-07. Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice.. https://doi.org/10.1101/2023.11.06.563831

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