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Different effects of antihypertensive drugs on endothelial dysfunction

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 endotheliummediated vasodilating effects. Calcium channel blockers are generally able to increase endotheliumdependent vasodilation in several vascular beds, in patients with essential hypertension, probably through multiple mechanisms. Most studies have shown that ACE 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 1 blockers on endothelial function in patients with essential hypertension, atherosclerosis or diabetes.There are data suggesting that an increased activity of the endothelin-1 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-1 receptor antagonists. However, to date no substantial clinical efficacy of endothelin-1 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.