Sustained hypoxia in mice increases parasympathetic but not sympathetic tone

Q: What are the key findings of this study?

Sustained hypoxia decreased baseline heart rate and increased the tachycardic response to methyl-atropine in mice.

Q: What is the clinical evidence from this study?

Population: Sustained hypoxia in conscious freely moving mice (n=30). Intervention: Sustained hypoxia (FiO2 0.1) followed by sequential pharmacological autonomic blockade (methyl-atropine, propranolol, prazosin) vs. Normoxia (FiO2 = 0.208 for 24h) followed by identical sequential pharmacological autonomic blockade. Primary outcome: Baseline heart rate (beats/min) (p=<0.0001).

Q: What does this research mean for the field?

Sustained hypoxia in mice increases cardiac parasympathetic tone and decreases baseline heart rate without altering sympathetic cardiac or vasomotor tone. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To characterize the cardiovascular and autonomic nervous system profile of conscious mice exposed to sustained hypoxia.

Juliana R. Souza; Mauro de Oliveira; Benedito H. Machado

doi:10.1016/j.crphys.2022.09.006

January 1, 2022Current Research in PhysiologyOpen Access

Sustained hypoxia in mice increases parasympathetic but not sympathetic tone

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Key result

Sustained hypoxia reduces baseline heart rate by ~132 bpm in mice, enhancing parasympathetic tone.

P<0.0001
n=30

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Why the study?

The autonomic profile of mice submitted to sustained hypoxia had not yet been fully evaluated.

Does 24-hour sustained hypoxia alter cardiac parasympathetic tone, cardiac sympathetic tone, and vascular sympathetic resistance in conscious freely moving mice compared to normoxic controls?

Key Points

To characterize the cardiovascular and autonomic nervous system profile of conscious mice exposed to sustained hypoxia.
Studied conscious freely moving control (n = 15) and sustained hypoxia (n = 15) mice.
Evaluated cardiac and vascular autonomic tones using two sequential pharmacological blockade protocols with methyl-atropine, propranolol, and prazosin.
Sustained hypoxia mice showed no significant change in baseline mean arterial pressure (116 ± 7 vs 112 ± 8 mmHg, P = 0,1617) but had significantly lower baseline heart rate (470 ± 78 vs 602 ± 62 beats. min −1; P < 0,0001) compared to controls.
Parasympathetic blockade with methyl-atropine produced a significantly greater tachycardic response in sustained hypoxia mice compared to controls (ΔHR: 182 ± 87 vs 95 ± 49 beats. min −1, P = 0.0359).
Sympathetic blockade of cardiac tone with propranolol (ΔHR: −200 ± 90 vs −192 ± 68 beats. min-1, P = 0.5358) and vasomotor tone with prazosin (ΔMAP: −14 ± 7 vs −16 ± 7 mmHg, P = 0.5835) yielded similar responses between groups.

Structured PICO

Does 24-hour sustained hypoxia alter cardiac parasympathetic tone, cardiac sympathetic tone, and vascular sympathetic resistance in conscious freely moving mice compared to normoxic controls?

P

Population

30 conscious freely moving male C57BL/6 mice (7-8 weeks old, ~25g) submitted to 24 hours of sustained hypoxia (FiO2 0.1) or normoxia (FiO2 0.208) followed by pharmacological autonomic blockade.

I

Intervention

Sustained hypoxia (SH) inside a chamber at a fraction of inspired O2 (FiO2) of 0.1 for 24 hours, followed by two sequential intravenous pharmacological autonomic blockade protocols: Protocol 1 (methyl-atropine 1 mg/kg, then propranolol 3 mg/kg, then prazosin 1 mg/kg at 10-min intervals) and Protocol 2 (propranolol 3 mg/kg, then methyl-atropine 1 mg/kg, then prazosin 1 mg/kg at 10-min intervals).

C

Comparator

Control mice maintained in a chamber under normoxic conditions (FiO2 = 0.208) for 24 hours, subjected to the exact same two sequential intravenous pharmacological autonomic blockade protocols.

O

Outcome

Baseline heart rate (HR) and mean arterial pressure (MAP), and changes in HR (ΔHR) and MAP (ΔMAP) in response to parasympathetic blockade (methyl-atropine), cardiac sympathetic blockade (propranolol), and vascular sympathetic blockade (prazosin) quantified 1 min during maximal response within 10 min post-injection.surrogate

Main Result

Absolute Event Rate: 470% vs 602%

p-value: p=<0.0001

Conscious mice subjected to 24-hour sustained hypoxia exhibit increased cardiac parasympathetic tone without increased cardiac or vasomotor sympathetic tone, explaining why mice—unlike rats—do not develop hypertension under sustained hypoxia.

Limitations

Only male mice were used in this study, requiring further experiments in female mice to verify possible sex differences
Preclinical animal model (C57BL/6 mice) which differs in autonomic and respiratory responses to sustained hypoxia compared to rats
Only male mice were used in this study; further experiments in female mice are required to verify possible sex differences in autonomic balance in response to sustained hypoxia.

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Implication

May explain species-specific resistance to hypoxic hypertension via parasympathetic dominance in mice; hypothesis-generating for autonomic mechanisms and human translation.

Abstract

The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.

Discussion

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Cite This Study

Souza et al. (2022) studied Sustained hypoxia in conscious freely moving mice (n=30). Sustained hypoxia (FiO2 0.1) followed by sequential pharmacological autonomic blockade (methyl-atropine, propranolol, prazosin) vs. Normoxia (FiO2 = 0.208 for 24h) followed by identical sequential pharmacological autonomic blockade was evaluated on Baseline heart rate (beats/min) (p=<0.0001). Sustained hypoxia decreased baseline heart rate and increased the tachycardic response to methyl-atropine in mice.

synapsesocial.com/papers/6a8c28e1ac7b7ae706e8cace https://doi.org/10.1016/j.crphys.2022.09.006

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Sustained hypoxia in mice increases parasympathetic but not sympathetic tone

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Sustained hypoxia in mice increases parasympathetic but not sympathetic tone

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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