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Current Pharmacological Approach to Restore Endothelial Dysfunction

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Endothelial dysfunction is characterized by an impairment of endothelium-dependent vasodilatation. It has been linked to each of the known atherogenic risk factors, including diabetes mellitus, hypertension, dyslipidaemia, cigarette smoking, menopause, etc. A number of recent studies have shown that the severity of endothelial dysfunction correlates with the development of coronary artery disease and predicts future cardiovascular events. Therefore, these findings strengthen the hypothesis that endothelial dysfunction may be an early stage of coronary atherosclerosis. This phenomenon primarily reflects an imbalance between the vasodilating (nitric oxide) and vasoconstrictor agents (endothelin- 1). Several invasive (intracoronary or intrabrachial infusions of vasoacting agents) and non-invasive techniques (assessment of flow mediated vasodilatation in the brachial artery by ultrasound) have been developed during the last few years to evaluate endothelial function in the coronary and peripheral circulation. This new methodology has allowed assessing the severity of the abnormalities in vascular function and their regression by several pharmacological and nonpharmacological interventions. It is likely that restoration of endothelial function can regress the atherosclerotic disease process and prevent future cardiovascular events. Most pharmacological interventions attempting to improve endothelial dysfunction targeted the risk factors linked to endothelial dysfunction: hypertension (ACE-inhibitors, calcium antagonists), dyslipidaemia (lipid-lowering agents) and menopause (estrogens). Nevertheless, several pharmacological agents have been suggested to achieve vascular protection through different mechanisms beyond their primary therapeutic actions: ACE-inhibitors, statins, third generation of beta-blockers (nebivolol), endothelium-derived nitric oxide synthesis (tetrahydrobiopterin, BH4) and antioxidants agents. In this review we will focus on the current pharmacological management of the endothelial dysfunction.

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Keywords: Endothelial dysfunction; atherosclerosis; coronary artery disease; endothelium; prognosis; treatment

Document Type: Research Article

Publication date: July 1, 2009

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  • Cardiovascular & Hematological Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Cardiovascular & Hematological Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Cardiovascular & Hematological medicinal chemistry.

    Cardiovascular & Hematological Agents in Medicinal Chemistry
    is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular & hematological drug discovery.
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