Objective: 

Polyarteritis nodosa in man is a necrotizing vasculitis of medium sized visceral and renal arteries of unknown origin. Hypertension is present in 30% of patients with polyarteritis nodosa. Until recently activation of the renin-angiotensin system in cases of polyarteritis nodosa with hypertension was thought to be secondary to renal involvement. In the present study we tested the hypothesis that (pro)renin can be also a primary cause for polyarteritis nodosa.

Methods: 

Cyp1a1ren-2 rats with or without telemetric device were induced with 0.125% I3C to elevate plasma prorenin levels. They were compared with non-induced rats and induced rats with telemetric device receiving captopril in the drinking water (N=6 each). During the course of the I3C-induction (10 - 11 weeks), the captopril dose was gradually elevated from 2 mg/100 ml to 25 mg/100 ml.

esults: Treatment of cyp1a1ren-2 transgenic rats with 0.125% I3C led to moderate hypertension (mean arterial pressure: 166.95.4 mmHg). 91% of the induced rats being chronically instrumented developed polyarteritis nodosa, but none of the other groups. A chronic necrotizing vasculitis was predominantly found in medium-sized arteries of the mesentery, pancreas and testes. The development of polyarteritis nodosa in induced rats with telemetric device could be prevented completely by the administration of captopril.

Conclusion: 

The renin-angiotensin system can play a primary role in the development of polyarteritis nodosa. Our findings give rise to the hope that the treatment of polyarteritis nodosa with inhibitors of the renin-angiotensin system may not only reduce blood pressure but may also directly inhibit the progression of the inflammatory disease.