Since endothelial dysfunction may significantly contribute to the pathophysiology of
hypertension and its complications, its modification seems to be a very attractive means to favourably affect the development of
atherosclerosis and cardiovascular events in hypertensive patients. However, not all
antihypertensive drugs consistently improve endothelial dysfunction. While first-generation beta-blockers showed contrasting or null effects on endothelial function, newer beta-blockers of the third generation, such as
carvedilol and
nebivolol, seem to be provided with specific endothelium-mediated vasodilating effects.
Calcium channel blockers are generally able to increase endothelium-dependent vasodilation in several vascular beds, in patients with
essential hypertension, probably through multiple mechanisms. Most studies have shown thatACE inhibitors favourably affect endothelial function mainly in the subcutaneous, epicardial and renal circulation, not only by inhibiting the effects of
angiotensin II on the endothelium, but also by enhancing
bradykinin-induced vasodilation, probably a hyperpolarization-related effect. On the other hand, discordant evidence is available about the effects of
angiotensin II receptor type I blockers on endothelial function in patients with
essential hypertension,
atherosclerosis or diabetes.There are data suggesting that an increased activity of the
endothelin- I system may play a role in the blunted endothelium-dependent vasorelaxation of hypertensive patients, an effect that could be contrasted by the use of
endothelin-I receptor antagonists. However, to date no substantial clinical efficacy of
endothelin-I receptor blockers has been shown in patients with
essential hypertension. Finally, other possibly useful compounds in restoring impaired endothelial function in
hypertension are some
antioxidant agents such as
vitamin C,
folic acid, the cofactor
tetrahydrobiopterin (BH4),
L-arginine and the drugs of the
statin class.