Endothelial effects of antihypertensive treatment: focus on irbesartan

The endothelium is characterized by a wide range of important homeostatic functions. It participates in the control of hemostasis, blood coagulation and fi brinolysis, platelet and leukocyte interactions with the vessel wall, regulation of vascular tone, and of blood pressure. Many crucial vasoactive endogenous compounds are produced by the endothelial cells to control the functions of vascular smooth muscle cells and of circulating blood cells. These complex systems determine a fi ne equilibrium which regulates the vascular tone. Impairments in endotheliumdependent vasodilation lead to the so called endothelial dysfunction. Endothelial dysfunction is then characterized by unbalanced concentrations of vasodilating and vasoconstricting factors, the most important being represented by nitric oxide (NO) and angiotensin II (AT II). High angiotensin-converting enzyme (ACE) activity leads to increased AT II generation, reduced NO levels with subsequent vasoconstriction. The net acute effect results in contraction of vascular smooth muscle cells and reduced lumen diameter. Furthermore, when increased ACE activity is chronically sustained, increase in growth, proliferation and differentiation of the vascular smooth muscle cells takes place; at the same time, a decrease in the anti-proliferative action by NO, a decrease in fi binolysis and an increase in platelets aggregation may be observed. AT II is then involved not only in the regulation of blood pressure, but also in vascular infl ammation, permeability, smooth muscle cells remodelling, and oxidative stress which in turn lead to atherosclerosis and increased cardiovascular risk. Given the pivotal role exerted by AT II in contributing to alteration of endothelial function, treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) may be of particular interest to restore a physiological activity of endothelial cells. In this view, the blockade of the renin-angiotensin system (RAS), has been shown to positively affect the endothelial function, beyond the antihypertensive action displayed by these compounds. In this review, attention has been specifi cally focused on an ARB, irbesartan, to examine its effects on endothelial function.