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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
- Source :
- Biochemical and Biophysical Research Communications. 434(2):210-216
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- medicine.medical_specialty
Dihydropyridines
Endothelium
Vasodilator Agents
Biophysics
Vasodilation
Aorta, Thoracic
Blood Pressure
medicine.disease_cause
Biochemistry
Mice
Calcium Channels, N-Type
Vascular relaxation
omega-Conotoxin GVIA
Internal medicine
Renin–angiotensin system
medicine
Animals
Endothelial dysfunction
Molecular Biology
Voltage-dependent calcium channel
Dose-Response Relationship, Drug
Chemistry
Angiotensin II
Macrophages
Hemodynamics
Cell Biology
Cilnidipine
medicine.disease
Calcium Channel Blockers
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Hypertension
cardiovascular system
Calcium
Amlodipine
Endothelium, Vascular
Reactive Oxygen Species
N-type Ca2+ channel
Oxidative stress
Biomarkers
medicine.drug
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 434
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....fe03e71bcce0e87e516e20806cd89184
- Full Text :
- https://doi.org/10.1016/j.bbrc.2013.03.040