Document Detail


The renin-angiotensin system as a primary cause of polyarteritis nodosa in rats.
MedLine Citation:
PMID:  19432815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polyarteritis nodosa is a necrotizing vasculitis of medium-sized arteries of unknown origin. Hypertension is present in 30% of patients with polyarteritis nodosa. In those cases, high renin levels are thought to be secondary to renal involvement. The present study was performed to identify causal factors of polyarteritis nodosa. In cyp1a1ren-2 transgenic rats, vasculitis of medium-sized arteries resembling classical polyarteritis nodosa can be induced. In this model, oral administration of indole-3-carbinol (I3C) activates the liver-specific cyp1a1 promoter, leading to prorenin expression in a dose-dependent manner. After the first 6 weeks of chronic induction with 0.125% I3C, the mean arterial pressure reached a plateau of about 170 mmHg. Ten out of 11 I3C-treated rats, which were chronically instrumented with a telemetric device to measure blood pressure, developed polyarteritis nodosa within 10 weeks of I3C treatment. I3C alone or instrumentation alone did not cause polyarteritis nodosa. The angiotensin-converting enzyme inhibitor captopril completely prevented the development of polyarteritis nodosa, indicating that local angiotensin II generation is a pathogenetic factor in this model. The renin-angiotensin system can play a primary role in the development of polyarteritis nodosa in rats.
Authors:
Barbara S Peters; Beate Kuttler; Andreas Beineke; Gerd Lorenz; Andrea Thiele; Oliver Nicolai; Rainer Rettig; John J Mullins; Jörg Peters
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-11
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  14     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-10-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1318-27     Citation Subset:  IM    
Affiliation:
Institute of Physiology, Department of Cardiovascular Medicine, University of Greifswald, Greifswald, Germany. bspeters@gmx.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Antineutrophil Cytoplasmic / metabolism
Antibodies, Antinuclear / metabolism
Antigens, CD3 / metabolism
Blood Pressure / drug effects
Body Weight / drug effects
Captopril / pharmacology
Cell Movement / drug effects
Cytochrome P-450 CYP1A1 / metabolism
Indoles / pharmacology
Male
Polyarteritis Nodosa / enzymology,  pathology,  physiopathology*
Rats
Rats, Transgenic
Renin / metabolism
Renin-Angiotensin System* / drug effects
T-Lymphocytes / drug effects
Weight Loss / drug effects
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antibodies, Antineutrophil Cytoplasmic; 0/Antibodies, Antinuclear; 0/Antigens, CD3; 0/Indoles; 0/Ren2 protein, rat; 62571-86-2/Captopril; 700-06-1/indole-3-carbinol; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 3.4.23.15/Renin

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