An Angiotensin-Converting Enzyme Inhibitor Suppresses the Expression of Vascular Cell Adhesion Molecule-1 and Production of Cytokines Induced in Activated Endothelial Cells

Quinaprilat, an angiotensin-converting enzyme (ACE) inhibitor, is commonly used for the therapy of hypertension, but the influence of ACE inhibitor for the atherogenesis has not been clear. Then we investigated the suppressive effect of ACE inhibitor on the expression of adhesion molecules and the production of cytokines which play an important role in the early development of atherosclerosis in endothelial cells (ECs). Quinaprilat treatment significantly reduced the activation of nuclear factor-kappaB (NF-kappaB), the surface expression of vascular cell adhesion molecule-1 (VCAM-1), the production of cytokines such as monocyte chemoattractant protein-1 and interleukin-6, and the number of mononuclear leukocytes adhering to ECs induced by tumor necrosis factor-alpha (TNF-alpha) and oxidized low-density lipoprotein (oxLDL). This suppressive effect was diminished by both a kinin B2 receptor antagonist and a nitric oxide synthase (NOS) inhibitor. These results indicated that quinaprilat reduced the activation of NF-kappaB under the stress of chemoattractants such as TNF-alpha and oxLDL through the increase of endothelial nitric oxide (NO) produced by activated endothelial nitric oxide synthase (eNOS) via a secondary accumulation of bradykinin in ECs. These results suggest an anti-atherogenic effect of ACE inhibitor.