Endothelium-Dependent Vasodilation in Hypertensive Patients

Endothelium plays a key role in modulating vascular tone through the production of vasodilator and vasoconstrictor substances. In animals, experimental hypertension is associated with endothelial dysfunction. In human hypertension, available evidence indicates the presence of a reduced basal production of nitric oxide and of an impaired vasodilation to the endothelium-dependent agonist acetylcholine or to the chemically related methacholine in the forearm and coronary vasculature. This abnormal response to endothelium-dependent agonists seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of cyclooxygenase-derived constrictor prostanoids. The reduced basal production of nitric oxide seems to be secondary to blood pressure increase while, at variance with observations in animals, it is possible that the impaired agonist-evoked endothelium-dependent vasodilation could be a primary phenomenon since it can be detected in young normotensive subjects with essential hypertensive parents. In addition aging can contribute to the endothelial dysfunction associated with essential hypertension. Finally, in essential hypertensive patients, non-pharmacological treatment through potassium administration seems to enhance endothelium-dependent vasodilation whereas, albeit scanty data are available, chronic effective pharmacological treatment, while restoring a normal basal production of nitric oxide, does not restore or at least improve the vascular response to endothelial agonists. Thus endothelial dysfunction is associated with essential hypertension and could play an important role in the pathophysiology and cardiovascular complications of the disease.