INTRODUCTION: The recent discovery of a specific receptor for renin/prorenin 
(PRR) has added new interest to the potential pharmacological actions of 
aliskiren, the first direct renin inhibitor.
MATERIALS AND METHODS: In the present study, to gain new insights into the 
pharmacological properties of aliskiren, we investigated the effect of aliskiren 
on PRR expression and activity in cultured human smooth muscle cells (HSMCs).
RESULTS: Co-incubation of HSMCs with angiotensinogen (ANG) (1.5 × 10(-7)M) and 
prorenin (10(-8)-10(-7)M) resulted in an efficient production (within 4h) of 
angiotensin I, almost completely inhibited by 10(-5)M aliskiren (-86.0 ± 14.0%). 
In HSMCs stimulated with both ANG and prorenin, a 24h incubation with aliskiren 
(10(-6)-10(-5)M) resulted in a concentration-dependent reduction of PRR mRNA 
levels (IC(50) 4.6 × 10(-6)M). The cell surface expression of PRR determined by 
flow cytometry analysis was also reduced after incubation with aliskiren in a 
concentration-dependent manner. The lower levels of PRR were associated with a 
reduced expression of TGF-β, PAI-1 and type I collagen mRNA.
CONCLUSIONS: These results suggest a direct pharmacological action of aliskiren 
on PRR expression and its signalling pathway in HSMCs. This reported action of 
aliskiren may reveal a new scenario of the pharmacological properties of 
aliskiren.