| Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats. | |
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MedLine Citation:
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PMID: 19620512 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation of the renin-angiotensin (Ang)-aldosterone system is involved in the pathology of vascular diseases. Although the blockade of the mineralocorticoid receptor protects against vascular diseases, its role in cerebral aneurysms remains to be elucidated. We treated female rats subjected to renal hypertension, increased hemodynamic stress, and estrogen deficiency for 3 months with the mineralocorticoid receptor blocker eplerenone (30 or 100 mg/kg per day) or vehicle (vehicle control). Eplerenone reduced the incidence of cerebral aneurysms and saline intake without lowering of the blood pressure. In the aneurysmal wall, the production of Ang II and nitrotyrosine was increased. The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased. Eplerenone brought about a reduction in these molecules, suggesting that mineralocorticoid receptor blockade suppresses cerebral aneurysm formation by inhibiting oxidative stress, inflammatory factors, local renin-Ang system activation, and saline intake. Other female rats implanted with pellets of the mineralocorticoid receptor agonist deoxycorticosterone acetate manifested a high incidence of cerebral aneurysm formation and the upregulation of molecules related to oxidative stress, inflammatory factors, and the local renin-Ang system; their saline intake was increased. We demonstrate that mineralocorticoid receptor activation at least partly contributes to the pathogenesis of cerebral aneurysms. |
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Authors:
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Yoshiteru Tada; Keiko T Kitazato; Tetsuya Tamura; Kenji Yagi; Kenji Shimada; Tomoya Kinouchi; Junichiro Satomi; Shinji Nagahiro |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-20 |
Journal Detail:
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Title: Hypertension Volume: 54 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-20 Completed Date: 2009-09-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 552-7 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Tokushima, Japan. yoshiteru.tada@hotmail.co.jp. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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blood Aldosterone Antagonists / pharmacology Angiotensin II / metabolism Animals Blood Pressure / drug effects Cerebral Arteries / drug effects, metabolism, pathology Chemokine CCL2 / genetics, metabolism Female Gene Expression / drug effects Hypertension, Renal / drug therapy, physiopathology Immunohistochemistry Intracranial Aneurysm / blood, physiopathology, prevention & control* NADPH Oxidase / genetics, metabolism Ovariectomy Oxidative Stress / drug effects Peptidyl-Dipeptidase A / genetics, metabolism RNA, Messenger / genetics, metabolism Rats Rats, Sprague-Dawley Receptors, Mineralocorticoid / antagonists & inhibitors*, physiology Renin-Angiotensin System / drug effects Reverse Transcriptase Polymerase Chain Reaction Spironolactone / analogs & derivatives*, pharmacology Tyrosine / analogs & derivatives, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Aldosterone Antagonists; 0/Ccl2 protein, rat; 0/Chemokine CCL2; 0/RNA, Messenger; 0/Receptors, Mineralocorticoid; 0/eplerenone; 11128-99-7/Angiotensin II; 3604-79-3/3-nitrotyrosine; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 55520-40-6/Tyrosine; EC 1.6.3.1/NADPH Oxidase; EC 3.4.15.1/Peptidyl-Dipeptidase A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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