Aliskiren (Novartis) is reported to act by binding to the protease Renin and inhibits the conversion of Angiotensinogen to Angiotensin I. This mechanism could prevent the incomplete blockade of the Renin-Angotensin-Aldosterone system by ACE-inhibitors and AT1-antagonists and leads at the bottom line to vasodilation. In a recent study we reported about vasoactive effects and augmentation of frequency during spontaneous activity in isolated vessels. Now we investigated the effects of Aliskiren in isolated cardiac preparations (Langendorff). Heparinized rat hearts were excised and the aorta was cannulated. Retrograde constant flow perfusion was maintained via peristaltic pump. Coronary restistance was measured by pressure and flow. Left ventricular contractility was examined by a balloon catheter and rhythm and cardiac frequency with ECG electrodes. During treatment with Aliskiren (10–50 mM), total coronary resistance increased up to 155% of control. Furthermore, frequency was reduced to 48% and contractility was increased. These unexpected results show a large similarity to those which can be observed during blockade of vascular and cardiac beta receptors.