Endothelial dysfunction and inhibition of converting enzyme

Abstract

Endothelial cells control the tone of the underlying vascular smooth muscle by secreting vasodilator substances (prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor). These vasodilator substances also contribute to the antithrombogenicity of the normal endothelium, and inhibit cellular growth. In coronary vascular disease, the ability of the endothelium to secrete vasodilator substances is reduced, while the propensity to release endothelium-derived contracting factors is increased. In particular, the reduced release of nitric oxide in response to aggregating platelets, thrombin and circulating catecholamines favours the occurrence of thrombosis and vasospasm, and plays a key role in the initiation of the atherosclerotic process. From the therapeutic point of view, the best available way to enhance the release of endothelium-derived nitric oxide and hyperpolarizing factor is to inhibit converting enzyme. This will protect endogenous bradykinin from breakdown and prolong its action on endothelial receptors.