Antioxidant and Cardioprotective Properties of the Sulphydryl Angiotensinconverting Enzyme Inhibitor Zofenopril

Abstract

Zofenopril, a new potent sulphydryl angiotensin-converting enzyme (ACE) inhibitor, is characterized by high lipophilicity, selective cardiac ACE inhibition, and antioxidant and tissue protective activities. In vitro and in vivo experiments suggest that zofenopril exerts antioxidant properties at clinically achievable tissue concentrations. In endothelial cells, zofenopril enhances nitric oxide production, attenuates atherosclerotic lesion development and inhibits adhesion molecule expression by reducing reactive oxygen species. These peculiar characteristics are reflected in the drug's cardioprotective activity, which has been shown to be greater than that of non-sulphydryl ACE inhibitors. Cardiac hypertrophy was also reduced by chronic zofenopril administration, independently of its blood pressure-reducing effect. ACE inhibitors with a sulphydryl group could have an advantage in improving vascular function and reducing cardiac impairment compared with non-sulphydryl-containing ACE inhibitors. This could explain zofenopril's remarkable clinical efficacy post-infarction, and potentially beneficial use in prevention and therapy of cardiovascular diseases, such as atherosclerosis, thrombosis and heart failure.