Dihydropyridine-based
calcium antagonists (DHPs) are widely used drugs for the treatment of
hypertension and
angina pectoris. We, along with others, have recently found that
nifedipine, one of the most widely used DHPs, inhibits apoptotic cell death of endothelial cells (ECs) as well as vascular
inflammation and subsequently improves endothelial function in patients with cardiovascular risk factors, including
hypertension and/or diabetes, thus slowing the development and progression of
atherosclerosis in these patients. Several papers have suggested that
nifedipine exerts beneficial metabolic effects in vivo through its anti-inflammatory properties as well. However, the underlying molecular mechanisms for the cardiometabolic actions of
nifedipine remain to be elucidated, because ECs do not possess voltage-operated
L-type calcium channels. Meanwhile, we have very recently found that
Bay w 9798, a
dihydropyridine structurally related to
nifedipine with no
calcium antagonistic ability, has anti-oxidative and anti-inflammatory properties in vitro. In this paper, we review the role of oxidative stress in the development of
vascular injury, especially focusing on the relationships between
advanced glycation end products-receptor system,
oxidized low-density lipoprotein and
tumor necrosis factor-alpha and vasculopathy. We further discuss the potential clinical utility of anti-oxidative properties of
nifedipine on various cardiometabolic disorders.