The cardiovascular actions of ACE inhibitors are not only mediated by a reduction of ANG II formation but also by the inhibition of the degradation of endogenous BK and related kinins. This is evidenced by the comparable effects of ACE inhibitors and exogenously added BK in different physiological and pathophysiological situations and by the observation that the specific B2 kinin receptor antagonist, icatibant, blocks the cardiovascular effects of ACE inhibitors as well as of BK in experimental models. The increase in local kinin concentrations by ACE inhibition exerts protective effects by activating signal transduction pathways which generate second messengers, such as cyclic GMP, via an increase in NO or cyclic AMP via an increase in PGI2. In our investigations many beneficial effects — biochemical and functional — of ACE inhibitors were observed even after sub-antihypertensive doses, consistent with the autocrine/paracrine role of the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS) and their interdependence.