| CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function. | |
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MedLine Citation:
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PMID: 20361197 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inhibition of the cannabinoid receptor CB(1) (CB(1)-R) exerts numerous positive cardiovascular effects such as modulation of blood pressure, insulin sensitivity and serum lipid concentrations. However, direct vascular effects of CB(1)-R inhibition remain unclear. CB(1)-R expression was validated in vascular smooth muscle cells (VSMCs) and aortic tissue of mice. Apolipoprotein E-deficient (ApoE-/-) mice were treated with cholesterol-rich diet and the selective CB(1)-R antagonist rimonabant or vehicle for 7 weeks. CB(1)-R inhibition had no effect on atherosclerotic plaque development, collagen content and macrophage infiltration but led to improved aortic endothelium-dependent vasodilation and decreased aortic reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of cultured VSMC with rimonabant resulted in reduced angiotensin II-mediated but not basal ROS production and NADPH oxidase activity. CB(1)-R inhibition with rimonabant and AM251 led to down-regulation of angiotensin II type 1 receptor (AT1-R) expression, whereas stimulation with the CB(1)-R agonist CP 55,940 resulted in AT1-R up-regulation, indicating that AT1-R expression is directly regulated by the CB(1)-R. CB(2)-R inhibition had no impact on AT1-R expression in VSMC. Consistently, CB(1)-R inhibition decreased aortic AT1-R expression in vivo. CB(1)-R inhibition leads to decreased vascular AT1-R expression, NADPH oxidase activity and ROS production in vitro and in vivo. This antioxidative effect is associated with improved endothelial function in ApoE-/- mice, indicating beneficial direct vascular effects of CB(1)-R inhibition. |
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Authors:
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Vedat Tiyerili; Sebastian Zimmer; Suzin Jung; Kerstin Wassmann; Claas P Naehle; Dieter Lütjohann; Andreas Zimmer; Georg Nickenig; Sven Wassmann |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-02 |
Journal Detail:
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Title: Basic research in cardiology Volume: 105 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-08-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
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Languages: eng Pagination: 465-77 Citation Subset: IM |
Affiliation:
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Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins E / deficiency Atherosclerosis / metabolism* Cells, Cultured Endothelium, Vascular / physiology* Female Mice Mice, Inbred C57BL Mice, Knockout Oxidative Stress* Piperidines Pyrazoles Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 / metabolism* Receptor, Cannabinoid, CB1 / antagonists & inhibitors, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Cannabinoid, CB1; 158681-13-1/rimonabant |
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