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The Journal of Physiological Sciences

, Volume 68, Issue 4, pp 441–454 | Cite as

β-Adrenergic signaling, monoamine oxidase A and antioxidant defence in the myocardium of SHR and SHR-mtBN conplastic rat strains: the effect of chronic hypoxia

  • Klara Hahnova
  • Iveta Brabcova
  • Jan Neckar
  • Romana Weissova
  • Anna Svatonova
  • Olga Novakova
  • Jitka Zurmanova
  • Martin Kalous
  • Jan Silhavy
  • Michal Pravenec
  • Frantisek Kolar
  • Jiri NovotnyEmail author
Original Paper

Abstract

The β-adrenergic signaling pathways and antioxidant defence mechanisms play important roles in maintaining proper heart function. Here, we examined the effect of chronic normobaric hypoxia (CNH, 10% O2, 3 weeks) on myocardial β-adrenergic signaling and selected components of the antioxidant system in spontaneously hypertensive rats (SHR) and in a conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of the more ischemia–resistant Brown Norway strain. Our investigations revealed some intriguing differences between the two strains at the level of β-adrenergic receptors (β-ARs), activity of adenylyl cyclase (AC) and monoamine oxidase A (MAO-A), as well as distinct changes after CNH exposure. The β2-AR/β1-AR ratio was significantly higher in SHR-mtBN than in SHR, apparently due to increased expression of β2-ARs. Adaptation to hypoxia elevated β2-ARs in SHR and decreased the total number of β-ARs in SHR-mtBN. In parallel, the ability of isoprenaline to stimulate AC activity was found to be higher in SHR-mtBN than that in SHR. Interestingly, the activity of MAO-A was notably lower in SHR-mtBN than in SHR, and it was markedly elevated in both strains after exposure to hypoxia. In addition to that, CNH markedly enhanced the expression of catalase and aldehyde dehydrogenase-2 in both strains, and decreased the expression of Cu/Zn superoxide dismutase in SHR. Adaptation to CNH intensified oxidative stress to a similar extent in both strains and elevated the IL-10/TNF-α ratio in SHR-mtBN only. These data indicate that alterations in the mitochondrial genome can result in peculiar changes in myocardial β-adrenergic signaling, MAO-A activity and antioxidant defence and may, thus, affect the adaptive responses to hypoxia.

Keywords

SHR Mitochondrial genome Myocardium β-adrenergic receptors Adenylyl cyclase Monoamine oxidase A Antioxidant defence Chronic hypoxia 

Notes

Acknowledgements

This work was supported by Grant 13-10267 from the Czech Science Foundation, Grant 1214214 from the Charles University Grant Agency, and by the institutional research projects no. 67985823 (Institute of Physiology, CAS) and SVV-260434/2017 (Charles University in Prague). MP was supported by Grants LL1204 (within the ERC CZ program) from the Ministry of Education, Youth and Sports and P301/12/0696 from the Czech Science Foundation.

Compliance with ethical standards

Conflict of interests

The authors have no conflict of interest to declare.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

12576_2017_546_MOESM1_ESM.docx (87 kb)
Supplementary material 1 (DOCX 87 kb)
12576_2017_546_MOESM2_ESM.docx (316 kb)
Supplementary material 2 (DOCX 315 kb)
12576_2017_546_MOESM3_ESM.docx (127 kb)
Supplementary material 3 (DOCX 127 kb)

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Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  • Klara Hahnova
    • 1
  • Iveta Brabcova
    • 1
  • Jan Neckar
    • 2
  • Romana Weissova
    • 2
  • Anna Svatonova
    • 2
  • Olga Novakova
    • 1
  • Jitka Zurmanova
    • 1
  • Martin Kalous
    • 3
  • Jan Silhavy
    • 2
  • Michal Pravenec
    • 2
  • Frantisek Kolar
    • 2
  • Jiri Novotny
    • 1
    Email author
  1. 1.Department of Physiology, Faculty of ScienceCharles UniversityPragueCzech Republic
  2. 2.Institute of PhysiologyCzech Academy of SciencesPragueCzech Republic
  3. 3.Department of Cell Biology, Faculty of ScienceCharles UniversityPragueCzech Republic

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