Taddei, S., Virdis, A., Ghiadoni, L. et al. High Blood Press Cardiovasc Prev (2003) 10: 19. doi:10.2165/00151642-200310010-00005
Endothelium plays a primary role in the local control of vascular function and structure. Thus endothelium-derived nitric oxide (NO) is not only a potent vasodilator but also inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. Essential hypertension is associated with endothelial dysfunction, which involves the enhanced production of oxygen free radicals, that can destroy NO and reduce its availability, and the release of endothelium-derived contracting factors, including prostanoids and endothelin-1.
Endothelial dysfunction in patients with essential hypertension is, at least in part, genetically determined and shows no correlation with blood pressure load, but is a promoter of atherosclerotic and thrombotic damage, which are typical complications of hypertension. In prospective studies, impaired endothelium-dependent vasodilation is associated with an increased incidence of cardiovascular events. Thus, endothelial dysfunction is often considered a target for cardiovascular treatment. However, endothelial function cannot yet be included among the surrogate endpoints that need to be measured for cardiovascular risk stratification in patients with essential hypertension because of the lack of validated tests. Currently, the tests available for assessing endothelium-dependent vasodilation are invasive or, if not invasive, do not have sufficient sensitivity and specificity for clinical practice. Moreover, despite considerable evidence that impaired endothelium-dependent vasodilation can be improved by the appropriate antihypertensive treatment, further large-scale clinical trials are required to prove conclusively whether reversal of endothelial dysfunction offers a clinical advantage in patients with essential hypertension. Only after a specific and affordable test has been validated, and definite evidence becomes available to demonstrate that endothelial dysfunction must be a target of pharmacological treatment, will the evaluation of endothelium-dependent vasodilation be included in the list of clinical examinations that define cardiovascular risk in patients with essential hypertension.