ENDOTHELIUM-DEPENDENT EFFECTS OF CONVERTING-ENZYME INHIBITORS

Angiotensin-converting enzyme (ACE) inhibitors were designed to preven t the vasoconstrictor influence of the activated renin-angiotensin sys tem. However, it has long been suspected that the vasodilator actions of these compounds are not entirely related to inhibition of the gener ation of angiotensin II. Bradykinin, which is rapidly degraded by ACE, stimulates the release of endothelium-derived vasodilator mediators, including nitric oxide, endothelium-derived hyperpolarizing factor, an d prostacyclin. These mediators do not contribute to the vasodilator e ffect of bradykinin in every arterial bed. However, the prevention by ACE inhibitors of the degradation of bradykinin-induces an augmentatio n of the production of these substances and thus potentiates the dilat ation evoked by the peptide. The existence of a local kallikrein-kinin system in the vascular wall has been demonstrated, and locally genera ted kinins contribute to the acute vasodilator actions of ACE inhibito rs. ACE inhibitors can potentiate endothelium-dependent dilatations ev oked by neurohumoral mediators that are not substrates for ACE. Thus. the vasodilator properties of ACE inhibitors not only reflect inhibiti on of the renin-angiotensin system but also depend on the enhanced pro duction of endothelium-derived mediators.