Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic rats: absence of prorenin-induced glomerulosclerosis

B. Peters, O. Grisk, B. Becher, H. Wanka, B. Kuttler, J. Ludemann, G. Lorenz, R. Rettig, J. J. Mullins, J. Peters

Research output: Contribution to journalArticlepeer-review


Objective Prorenin has been associated with cardiovascular disease and the development of glomerulosclerosis via a renin/prorenin receptor. In cyp1a1ren-2 transgenic rats, prorenin levels and arterial pressure can be increased by oral administration of indole3-carbinol (I3C). The transgenic strain has been used as a model of malignant hypertension. Methods The present study was designed to test the hypotheses that (i) low doses of I3C would result in dose-dependent sustained increases in arterial pressure without signs of malignancy, making cyp1a1ren-2 transgenic rats a useful model to study nonmalignant hypertension, and (ii) cyp1a1ren-2 transgenic rats would develop glomerulosclerosis when they were chronically exposed to 0.125% I3C in their diet. Results I3C treatment for 2 weeks resulted in increases of plasma prorenin concentrations and arterial pressure in a dose-dependent manner. Rats thrived well over a period of 12 weeks on dietary I3C concentrations (wt/wt) of 0.125%. Plasma prorenin concentration rose from 0.1 +/- 0.1mg to 17.9 +/- 5.0mg angiotensin I/ml per h ( P <0.01) and mean arterial pressure increased to a plateau of 170 +/- 5 mmHg (P <0.001) between weeks 6 and 12. After 12 weeks of 0.125% I3C, rats exhibited moderate hypertensive renal vasculopathy, but no histological signs of glomerulosclerosis. Conclusions The cyp1a1ren-2 transgenic rat model allows for chronic dose-dependent titration of arterial pressure by a simple and non-invasive intervention, making this strain a useful model to study malignant and nonmalignant arterial hypertension. High circulating prorenin levels per se do not cause glomerulosclerosis.
Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalJournal of Hypertension
Issue number1
Publication statusPublished - Jan 2008

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