Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice
Open accessAbstract
N-type voltage-dependent Ca(2+)channels (VDCCs), expressed predominantly in the nervous system, play pivotal roles in sympathetic regulation of the circulatory system. Although N-type VDCCs are also reportedly expressed in the vasculature, their pathophysiological role is obscure. We demonstrated that oxidative stress-related endothelial dysfunction induced by angiotensin (Ang) II is suppressed in mice lacking the N-type VDCC α1B subunit (Cav 2.2). Impairment of endothelium-dependent relaxation of the thoracic aorta observed following Ang II treatment in wild-type (WT) mice was significantly attenuated in the Ang II-treated Cav 2.2-deficient mice, despite the comparable increase of the blood pressure in the two groups of mice. The thoracic aorta of the Cav 2.2-deficient mice showed a smaller positive area of oxidative stress markers as compared to the WT mice. The Ang II-induced endothelial dysfunction was also suppressed by cilnidipine, an L/N-type VDCC blocker, but not by amlodipine, an L-type VDCC blocker; however, this unique effect of cilnidipine was completely abolished in the Cav 2.2-deficient mice. Furthermore, selective inhibition of N-type VDCCs by ω-conotoxin GVIA dramatically suppressed the production of reactive oxygen species (ROS) as well as agonist-induced Ca(2+) influx in the vascular endothelial cells. These results suggest that N-type VDCCs expressed in the vascular endothelial cells contribute to ROS production and endothelial dysfunction observed in Ang II-treated hypertensive mice.
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L-type channels are linked with oxidation of thiol groups, resulting in changed entry of calcium into the cytoplasm.
“L-type channels are linked with the oxidation of thiol groups resulting in changed entry of calcium in the cytoplasm (Nishida et al. 2013).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Nishida et al. 2013
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- Authors
- Nishida, M., Ishikawa, T., Saiki, S., Sunggip, C., Aritomi, S., Harada, E., Kuwahara, K., Hirano, K., Mori, Y., & Kim-Mitsuyama, S.
- Affiliations
- Kyushu University (JP)
- Ajinomoto (Japan) (JP)
- Kyoto University (JP)
- ORCID
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 434
- Issue
- 2
- Pages
- 210-216
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2086208708
- Cited by
- 18
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Uehara Memorial Foundation
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- CaV2.2, endothelial dysfunction, angiotensin II, oxidative stress, reactive oxygen species, cilnidipine, omega-conotoxin GVIA, vascular endothelial cells, thoracic aorta, hypertension, endothelium-dependent relaxation, calcium influx
- MeSH terms
- Angiotensin II, Animals, Aorta, Thoracic, Blood Pressure, Calcium, Calcium Channel Blockers, Dihydropyridines, Dose-Response Relationship, Drug, Endothelium, Vascular, Hemodynamics, Hypertension, Macrophages, Vasodilation, Vasodilator Agents, Biomarkers, Amlodipine, Reactive Oxygen Species, Oxidative Stress, Calcium Channels, N-Type, omega-Conotoxin GVIA, Mice
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