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Anti-hypertensive effect of hydrogen peroxide acting centrally

Hypertension Research volume 43, pages 1192–1203 (2020)Cite this article

Abstract

Intracerebroventricular (icv) injection of hydrogen peroxide (H2O2) or the increase of endogenous H2O2 centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with H2O2 injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5–10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, H2O2 (5 μmol/1 μl) or ATZ (5 nmol/1 μl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with H2O2 icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (−10 to −15 mmHg) in 2K1C hypertensive rats treated with H2O2 icv and ATZ iv alone or combined and in SHRs treated with H2O2 icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous H2O2 acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.

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Acknowledgements

The authors thank Silas Pereira Barbosa for expert technical assistance, Silvana A.D. Malavolta and Carla D.M.D. Souza for secretarial assistance, and Ana V. de Oliveira and Mikail Douglas dos Santos for animal care. This research was supported by funding from Brazilian public research agencies (Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (2013/05189-4 and 2015/23467-7) and Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (302258/2015-9).

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  1. Department of Physiology and Pathology, Dentistry School, São Paulo State University (UNESP), Araraquara, SP, Brazil

    Mariana R. Lauar, Débora S. A. Colombari, Eduardo Colombari, Patrícia M. De Paula, Laurival A. De Luca Jr. & José V. Menani

  2. School of Medicine, Pharmacy and Biomedicine, Pontifical Catholic University of Goias, Goiania, GO, Brazil

    Graziela T. Blanch

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Lauar, M.R., Blanch, G.T., Colombari, D.S.A. et al. Anti-hypertensive effect of hydrogen peroxide acting centrally. Hypertens Res 43, 1192–1203 (2020). https://doi.org/10.1038/s41440-020-0474-5

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