The cyp1a1 ren-2 rat is a model of prorenin induced hypertension. In this model liver specific expression of ren-2 prorenin and hypertension can be reversibly induced by administration of Indole-3-Carbinole (I3C) with the food. Malignant hypertension occurs within two weeks using 0.3% I3C, accompanied by severe weight loss and polyuria. The present study was performed to investigate whether chronic non-malignant hypertension can be established without weight loss and polyuria. Results: Rats thrived well on 0.125 % I3C despite chronic mean arterial pressure of about 180 mmHg (radio telemetry). After 12 weeks of treatment, rats showed moderate cardiac hypertrophy as well as hypertensive vasculopathy. Plasma prorenin concentrations rose from 0.07±0.08 to 17.9±5 mgANGI/ml/hr selectively in I3C treated transgenic rats (p<0.001). In contrast, plasma renin concentrations were markedly suppressed in I3C treated transgenic rats (from 0.3±0.11 to. 0.09±0.01 mgAI/ml/hr; p<0.01) but remained unchanged in untreated transgenic controls (0.31±0.11 vrs. 0.24±0.1 mgAI/ml/hr; n. s.) as well as in I3C treated non-transgenic rats (0.13±0.02 vrs. 0.14±0.02; n. s.). Conclusions: The cyp1a1ren-2 transgenic rat is a useful model for chronic hypertension with moderate end organ damage. Furthermore the model provides a tool to study the effects of circulating prorenin.