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Hypoxic training improves blood pressure, nitric oxide and hypoxia-inducible factor-1 alpha in hypertensive patients

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Abstract

Purpose

To examine the effects of intermittent hypoxic breathing at rest (IHR) or during exercise (IHT) on blood pressure and nitric oxide metabolites (NOx) and hypoxia-inducible factor-1 alpha levels (HIF-1α) over a 6-week period.

Methods

47 hypertensive patients were randomly allocated to three groups: hypertensive control (CON: n = 17; IHR: n = 15 and IHT: n = 15. The CON received no intervention; whereas, IH groups received eight events of hypoxia (FIO2 0.14), and normoxia (FIO2 0.21), 24-min hypoxia and 24-min normoxia, for 6 weeks. The baseline data were collected 2 days before the intervention; while, the post-test data were collected at days 2 and 28 after the 6-week intervention.

Results

We observed a significant decrease of the SBP in both IH groups: IHR (− 12.0 ± 8.0 mmHg, p = 0.004 and − 9.9 ± 8.8 mmHg, p = 0.028, mean ± 95% CI) and IHT (− 13.0 ± 7.8 mmHg, p = 0.002 and − 10.0 ± 8.4 mmHg, p = 0.016) at days 2 and 28 post-intervention, respectively. Compared to CON, IHR and IHT had increased of NOx (IHR; 8.5 ± 7.6 μmol/L, p = 0.031 and IHT; 20.0 ± 9.1 μmol/L, p < 0.001) and HIF-1α (IHR; 170.0 ± 100.0 pg/mL, p = 0.002 and IHT; 340.5 ± 160.0 pg/mL, p < 0.001). At 2 days post-intervention, NOx and HIF-1α were negatively correlated with SBP in IHT.

Conclusion

IH programs may act as an alternative therapeutic strategy for hypertension patients probably through elevation of NOx and HIF-1α production.

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Abbreviations

ATS:

American Thoracic Society

CI:

Confidence interval

EDTA:

Ethylenediaminetetraacetic acid

FIO2 :

Fraction inspired of oxygen

GEE:

Generalized estimating equation model

HIF-1α:

Hypoxia-inducible factor-1 alpha levels

IHR:

Intermittent hypoxic breathing at rest

IHT:

Intermittent hypoxic training

JNC 8:

The Eighth Joint National Committee

MDA:

Malondialdehyde

MWT:

Minute walk test

MWCO:

Molecular weight cut-off

MWD:

Minute walk distance

NOx:

Nitric oxide metabolites

RPD:

Rating of perceived of dyspnea

RPE:

Rating of perceived of exertion

TMB:

Tetramethylbenzidine

References

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Acknowledgements

The authors would like to thank all patients for their valuable time. We would like to thank the Exercise and Sport Sciences Developing and Research Group to support the biochemistry laboratory.

Funding

The study was financially supported by grants from the Khon Kaen University in collaboration with the National Research Council of Thailand (NRCT) and an Invitation Research Grant (Grant number IN61142), Faculty of Medicine, Khon Kaen University. Miss Nattha Muangritdech was partly supported by a Postgraduate Study Support Grant of Faculty of Medicine, Khon Kaen University, Thailand.

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Authors and Affiliations

Authors

Contributions

NM (first author) and AM conceived and designed the trial. NM (first author), PP, WS, KS, NM conducted experiments. PP performed the molecular laboratory tests, PW provided support throughout the experiment. NM and AM analyzed data. NM, AM and HM wrote the manuscript. All authors read and edited manuscript. AM and HM approved the final version of manuscript for publication.

Corresponding author

Correspondence to Apiwan Manimmanakorn.

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Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by I. Mark Olfert.

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Muangritdech, N., Hamlin, M.J., Sawanyawisuth, K. et al. Hypoxic training improves blood pressure, nitric oxide and hypoxia-inducible factor-1 alpha in hypertensive patients. Eur J Appl Physiol 120, 1815–1826 (2020). https://doi.org/10.1007/s00421-020-04410-9

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  • DOI: https://doi.org/10.1007/s00421-020-04410-9

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