The renin-angiotensin system as a primary cause of polyarteritis nodosa in rats.
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.
Institute of Physiology, Department of Cardiovascular Medicine, University of Greifswald, Greifswald, Germany. bspeters@gmx.de
Barbara S
BS
Peters
Beate
B
Kuttler
Andreas
A
Beineke
Gerd
G
Lorenz
Andrea
A
Thiele
Oliver
O
Nicolai
Rainer
R
Rettig
John J
JJ
Mullins
Jörg
J
Peters
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D000974:Antibodies, Antinuclear / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D017252:CD3 Complex / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010488:Polyarteritis Nodosa / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D019268:Antibodies, Antineutrophil Cytoplasmic; D000974:Antibodies, Antinuclear; D017252:CD3 Complex; D007211:Indoles; C535029:Ren2 protein, rat; D002216:Captopril; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D012083:Renin