Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice

Motohiro Nishida, Tatsuya Ishikawa, Shota Saiki, Caroline Sunggip, Shizuka Aritomi, Eri Harada, Koichiro Kuwahara, Katsuya Hirano, Yasuo Mori, Shokei Kim-Mitsuyama

Research output: Contribution to journalArticle

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Abstract

N-type voltage-dependent Ca2+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 Ca2+ 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.

Original languageEnglish
Pages (from-to)210-216
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume434
Issue number2
DOIs
Publication statusPublished - May 3 2013

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Oxidative stress
Endothelial cells
Angiotensin II
Oxidative Stress
Endothelial Cells
Electric potential
Thoracic Aorta
Reactive Oxygen Species
Conotoxins
Amlodipine
Blood pressure
Neurology
Cardiovascular System
Nervous System
Endothelium
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice. / Nishida, Motohiro; Ishikawa, Tatsuya; Saiki, Shota; Sunggip, Caroline; Aritomi, Shizuka; Harada, Eri; Kuwahara, Koichiro; Hirano, Katsuya; Mori, Yasuo; Kim-Mitsuyama, Shokei.

In: Biochemical and Biophysical Research Communications, Vol. 434, No. 2, 03.05.2013, p. 210-216.

Research output: Contribution to journalArticle

Nishida, Motohiro ; Ishikawa, Tatsuya ; Saiki, Shota ; Sunggip, Caroline ; Aritomi, Shizuka ; Harada, Eri ; Kuwahara, Koichiro ; Hirano, Katsuya ; Mori, Yasuo ; Kim-Mitsuyama, Shokei. / Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 434, No. 2. pp. 210-216.
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