Aliskiren (Novartis) is reported to lower blood pressure by inhibition of the protease Renin that converts Angiotensinogen toAngiotensinI.In a recent study we have demonstrated, that Aliskiren exerts direct effects on vascular smooth muscle. Hepatic portal vein is a blood vessel, that has been reported to consist of smooth muscle cells (VSM), nerve terminals (NT), interstitial Cajal-like cells (ICC) and endothelial cells (ET). For other blood vessels, the existence of ICC is unclear. In this study, we investigated the possible site of action of Aliskiren in rat Aorta and Portal vein to find out the major sites of action of this drug.

Using a paradigm that includes electrical field stimulation, TTX to suppress NT activity and thermal uncoupling of ICC, it could be shown, that Aliskiren can exert its direct effects on VSM. This is more expressed in Aorta than in portal vein. Furthermore, in rat portal vein, activation of ICC is strongly dependent on NT activity. The increase of the excitation frequency during Aliskiren under control conditions was only partial seen under TTX, indicating that one major interaction site of Aliskiren on NT is highly likely.