Pharmacological interventions to prevent vascular endothelial dysfunction: Future directions

Endothelium forms an innermost lining of blood vessel and it regulates the vascular tone and permeability. A healthy vascular endothelium is antiatherogenic in nature because of its properties such as inhibition of platelet aggregation, adhesion cascades, smooth muscle cell proliferation and leukocyte adhesion. Vascular endothelial dysfunction (VED) is associated with reduced synthesis and release of nitric oxide, proinflammatory and prothrombotic properties followed by diminished vasodilation. VED has been implicated in the pathogenesis of artherosclerosis, hypertension, myocardial infarction, heart failure, renal failure and stroke. Various pharmacological interventions such as angiotensin converting enzyme (ACE) inhibitors, statins, insulin sensitizers, L-arginine as well as agents that target endothelial nitric oxide synthase (eNOS) "coupling" such as folates or tetrahydrobiopterin (BH4) have been noted to improve the function of vascular endothelium. In this review, we discussed various recently developed pharmacological interventions to improve the function of endothelium. Moreover, the novel targets sites involved in the pathogenesis of vascular endothelial dysfunction have been delineated.