Vascular endothelial dysfunction and pharmacological treatment

Abstract

The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease.

Keywords: Endothelial dysfunction; Endothelium-dependent vasodilation; Endothelial nitric oxide synthase; Inflammation; Nitric oxide; Pharmacological treatment; Reactive nitrogen species; Reactive oxygen species; Risk factors

Core tip: The endothelium is involved in the regulation of vascular tone and permeability, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Cardiovascular risk factors cause vascular endothelial dysfunction through impairing endothelium-derived vasodilators, enhancing endothelium-derived vasoconstrictors, producing reactive oxygen species and reactive nitrogen species, activating inflammatory and immune reactions and promoting thrombosis. Among these mechanisms, a reduction in nitric oxide bioavailability plays a central role in the development and progression of endothelial dysfunction. A variety of currently used or investigational drugs exert endothelial protective effects according to specific mechanisms underlying endothelial dysfunction of the disease.