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  Theme-based Research Scheme–Call for Preliminary Proposals

  Launch of New Joint Research Schemes

  Nanotherapeutics in Angiogenesis: Synthesis and in Vivo Assessment of Drug Efficacy and Biocompatibility in the Zebrafish Embryos

  Nimodipine suppresses chemokine release via inhibition of adenosine uptake in endothelial cells

  DNA-binding Activities of Some Alkaloids from Chinese Medicinal Herbs

  Development of a High Performance Liquid Chromatographic Method for the Quality Control of Rhizoma Smilacis Glabrae and its Derived Products

  Interactions between UGT isoenzymes and MRP transporters during the oral absorption process of Baicalein

  Gender Differences in the Regulation of Endothelium-Dependent Contracting Factor

  Areas of Excellence Scheme Project: Introducing the Work of the Hong Kong Institute of Economics and Business Strategy

  Areas of Excellence of Scheme Project: Building excellence in plant and agricultural biotechnology research

  RGC Collaborative Research Fund – Layman Summaries of Projects Funded in 2009/10 Exercise


Atherosclerosis is a common disease in which the artery wall thickens as a result of a build-up of fatty materials. The narrowing of arteries caused by atherosclerosis can significantly reduce the blood supply to vital organs. The complications of advanced atherosclerosis include heart attack and stroke, which are the major killers in modern society. While many clinicians consider the use of lipid-lowering agents like statins as the main strategy to prevent atherosclerosis, the combination of dihydropyridine-type calcium channel blockers (DHP) (a blood vessel dilator used in the treatment of patients with angina and hypertension) and statins has been shown to produce an additional 60% reduction of atherosclerosis compared with that observed with statins alone. Therefore, the effects of DHP on atherosclerosis are promising. 

The inflammation of endothelial cell layers is regarded as an initial and the most critical step in the development of atherosclerosis. Biochemical assays show that nimodipine, a DHP which is more commonly used in the prevention/treatment of cerebral vasospasm, can reduce the release of proinflammatory cytokines and chemokines from endothelial cells. These results indicate that nimodipine exerts anti-inflammatory effect on endothelial cells. Among the DHP, the anti-inflammatory effect of nimodipine is the most potent. Most of the DHP are known to reduce reactive oxygen species formation. However, nimodipine exerts no antioxidant effect. We measured the adenosine transport into endothelial cells by using radioactive adenosine as a tracer. Our data shows that

nimodipine can inhibit the equilibrative nucleoside transporter type-1 (ENT-1) , thereby increasing the local concentration of adenosine in the vicinity of adenosine receptors on endothelial cells. The increased stimulation of adenosine receptors may be a mechanism underlying the anti-inflammatory effect of nimodipine. The mechanism by which nimodipine inhibits ENT-1 has been further investigated. The study of structure-activity relationship reveals that the inhibitory potency of nimodipine is closely associated with the presence of the 4-aryl ring, as well as the bulkiness of ester groups at the C-3 and C-5 positions. Nimodipine is a non-competitive inhibitor of ENT-1, probably working through the reversible interactions with allosteric sites of ENT-1. The nimodipine binding site is probably located in the transmembrane domains 3-6 on ENT-1.

It is hoped that the findings in this study can add new knowledge on treatment of atherosclerosis. The anti-inflammatory properties of nimodipine on endothelial cells may provide extra benefit in preventing the atherosclerotic type of stroke. Understanding the structural determinants involved in the interaction between ENT-1 (which is the major adenosine transporter in endothelial cells) and nimodipine may facilitate the design and development of novel cardiovascular protective drugs.

Dr George Pak-Heng Leung
Department of Pharmacology and
The University of Hong Kong