Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries
Open accessAbstract
Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N ω-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I–V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.
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Mitochondria extracted from brain, liver, and cerebral arteries of female rodents displayed more efficient oxidative phosphorylation than in males.
“mitochondria extracted from brain, liver, and cerebral arteries of female rodents displayed more efficient oxidative phosphorylation than in males”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [122]
Under physiological conditions, sex-specific differences in mitochondrial respiration, bioenergetics, and reactive oxygen species production have been reported in both human and animal studies.
“Under physiological conditions, sex-specific differences in mitochondrial respiration, bioenergetics, and reactive oxygen species production have been reported in both human and animal studies.”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [122]
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Self-citationYang, C., Dave, D. D., Boovarahan, S. R., Shimada, S., Geurts, A. M., Dash, R. K., & Cowley, A. W. (2025) · Function · doi:10.1093/function/zqaf045 · Cited by 2 · see citing works
Junctions, Transporters, and Interactions of Endothelial Cells: Regulation by Ethanol
Mandyam, C. D., Vandekerkhoff, A., Jung, S., Kharidia, D., Ponomarev, I., & Kisby, B. R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27062695 · Cited by 1 · see citing works
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Pislaru, A., & Haas, T. L. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1830278 · Cited by 1 · see citing works
Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion
Urushihata, T., Takahashi, M., Shimojo, M., Takado, Y., Nitta, N., Tajima, Y., Masamoto, K., Kanno, I., 冨田, 裕., Sahara, N., et al. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251328971 · Cited by 1 · see citing works
Huang, X., Li, J., Huang, Z., Wang, Y., Dan-qing, Y., & He, X. (2025) · Vessel Plus · doi:10.20517/2574-1209.2025.94
- Authors
- Rutkai, I., Dutta, S., Katakam, P. V., & Busija, D. W.
- Affiliations
- Tulane University (US)
- Corresponding author
- Rutkai, Ibolya
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2015-11
- Volume
- 309
- Issue
- 9
- Pages
- H1490-H1500
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC4666975
- OpenAlex
- W1927834555
- Cited by
- 37
- References
- 59
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 4
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (AHA) (15POST23040005, 14SDG20490359)
- Louisiana Board of Regents (Board of Regents) (LEQSF(2014-17)-RD-A-11)
- NHLBI (HL-077731, HL093554)
- Louisiana board of Regents Endowed Chairs for Eminent Scholars
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- mitochondrial respiration, cerebral arteries, sex differences, nitric oxide, nitric oxide synthase inhibition, diazoxide, vasodilation, mitochondrial proteins, voltage-dependent anion channel, ATP production, proton leak, spare respiratory capacity
- MeSH terms
- Adenosine Triphosphate, Animals, Cerebral Arteries, Diazoxide, Enzyme Inhibitors, Female, Male, Mitochondria, Nitric Oxide, Sex Factors, Vasodilator Agents, Rats, Sprague-Dawley, Nitric Oxide Synthase, Cell Respiration, NG-Nitroarginine Methyl Ester, Mitochondrial Proteins, Endothelium-Dependent Relaxing Factors, Rats
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