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Angiotensin-converting enzyme inhibition and endothelial dysfunction: focus on ramipril

F. Enseleit, T.F. Lüscher and F. Ruschitzka1

University Hospital, Cardiovascular Center Cardiology, Zürich, Switzerland

1 Frank Ruschitzka, MD, FESC, Assistant Professor, University Hospital, CH-8091 Zürich, Switzerland.

Abstract

Endothelial cells are strategically located between the circulating blood and the vascular smooth muscle. Through release of numerous vasoactive substances, they are crucially involved in regulating the functions of vascular smooth muscle and circulating blood cells. Important endothelium-delivered vasodilators include prostacyclin, bradykinin, endothelium-derived hyperpolarising factor, and nitric oxide. Nitric oxide inhibits cellular growth and migration, and acts in concert with prostacyclin to exert potent antiatherogenic and antithrombotic effects. These effects are counterbalanced by endothelial vasoconstrictors, such as reactive oxygen species, endothelin-1, and angiotensin II, which exert pro-thrombotic, inflammatory, and growth-promoting properties. Cardiovascular risk factors cause cardiovascular disease by causing endothelial dysfunction; thus, modern therapeutic strategies focus on preserving or restoring endothelial integrity. In addition to their role in inhibiting the renin-angiotensin system, angiotensin-converting enzyme (ACE) inhibitors prolong the half-life of bradykinin and stabilize the bradykinin receptor linked to formation of nitric oxide. Chronic ACE inhibition improves endothelial function in patients with cardiovascular risk. This may explain why patients treated with ACE inhibitors experience a greater cardiovascular benefit than is attributable to the decrease in blood pressure. Whether and to what degree improvement of endothelial dysfunction translates into clinical benefits for patients with cardiovascular disease remains to be determined.

Key Words: ACE inhibitors • cardiovascular disease • endothelial function • ramipril

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