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Perinatal hypoxia weakens anticontractile influence of NO in rat arteries during early postnatal period

Abstract

Background

Perinatal hypoxia affects a lot of neonates worldwide every year, however its effects on the functioning of systemic circulation are not clear yet. We aimed at investigation the effects of perinatal hypoxia on the second day of life on the functioning of the rat systemic vasculature in early postnatal period.

Methods

2-day-old male rat pups were exposed to normobaric hypoxia (8% O2, 92% N2) for 2 hours. At the 11-14 days cutaneous (saphenous) arteries were isolated and studied by wire myography and Western blotting.

Results

Hypoxia weakened the contribution of anticontractile influence of NO, but did not affect the contribution of Rho-kinase or Kv7 channels to the contraction to α1-adrenergic agonist methoxamine. The content of eNOS and protein kinase G were not altered by hypoxic conditions.

Conclusion

Perinatal hypoxia in rats at the second day of life leads to the decrease of anticontractile effect of NO in the systemic arteries in early postnatal ontogenesis (at the age of 11-14 days). Decreased anticontractile effect of NO can be the reason for insufficient blood supply and represent a risk factor for the development of cardiovascular disorders.

Impact

  • The mechanisms of perinatal hypoxia influences on systemic circulation are almost unknown.

  • We have shown that perinatal hypoxia weakens anticontractile influence of nitric oxide in early postnatal period.

  • The influence of perinatal hypoxia on systemic circulation should be taken into account during treatment of newborns suffered from the lack of oxygen.

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Fig. 1: Perinatal hypoxia at the age of 2 days does not affect the basic vasomotor characteristics of the saphenous artery in 11-14-day-old rat pups.
Fig. 2: Influence of perinatal hypoxia at the age of 2 days on the contribution of regulatory pathways in arteries of 11-14-day-old rat pups.
Fig. 3: Perinatal hypoxia at the age of 2 days does not affect the protein content of Rho-kinase II, eNOS and protein kinase G in saphenous arteries of 11-14-day-old rat pups.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Dr. E. A. Sebentsova and Dr. N. G. Levitskaya for providing access for facility to model hypoxia. The part of equipment used in the study was provided by MSU within the framework of federal project “The development of infrastructure for science and education” (Agreement \({{{{{\rm{N}}}}}}\underline{{{{{\rm{o}}}}}}\) 161).

Funding

The study was supported by Russian Science Foundation (Project \({{{{{\rm{N}}}}}}\underline{{{{{\rm{o}}}}}}\) 21-75-10036).

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Contributions

Conceptualization and experimental design (A.A.Sh., D.K.G.), data collection (A.A.Sh., D.D.Kh., S.D.S., M.A.Kh., A.A.B., D.K.G.), data processing (A.A.Sh., D.K.G.), manuscript draft writing (A.A.Sh., D.K.G.).

Corresponding author

Correspondence to Dina K. Gaynullina.

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Shvetsova, A.A., Khukhareva, D.D., Simonenko, S.D. et al. Perinatal hypoxia weakens anticontractile influence of NO in rat arteries during early postnatal period. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03062-1

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