Angiotensin converting enzyme inhibitors and vascular protection in hypertension.

Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances regulating the function of vascular smooth muscle and circulating blood cells. Endothelium-derived vasodilators include prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor. In particular, nitric oxide inhibits cellular growth and migration. In concert with prostacyclin, nitric oxide exerts potent antiatherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by vasoconstrictors, such as angiotensin II and endothelin (ET)-1, both of which exert prothrombotic and growth-promoting properties. In hypertension, elevated blood pressure causes vascular disease by inducing endothelial dysfunction. Hence, modern therapeutic strategies in human hypertension focus on preserving or restoring endothelial integrity. Beyond inhibiting the renin-angiotensin system, angiotensin-converting enzyme (ACE) inhibitors diminish the inactivation of bradykinin, thus leading to an augmentation of nitric oxide release. In addition, the compounds stabilize the B2-receptor, and reduce oxidative stress and tissue ET-1 levels. In patients with coronary artery disease, chronic ACE inhibition improves endothelial function. Further clinical studies are already under way which will prove whether these beneficial vascular effects of ACE inhibitors on endothelial dysfunction result in a clinical benefit for patients with hypertension.