Current pharmacological approach to restore endothelial dysfunction.
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 non-pharmacological 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.
Dobarro
D
D
Interventional Cardiology Unit, Planta 1a Diagonal, University Hospital La Paz, 28046 Madrid, Spain.
Gómez-Rubín
M C
MC
Sanchez-Recalde
A
A
Moreno
R
R
Galeote
G
G
Jimenez-Valero
S
S
Calvo
L
L
López de Sá
E
E
López-Sendón
J L
JL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D004727:Endothelium / Q000187:drug effects* / Q000503:physiopathology*; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D009566:Nitrates / Q000494:pharmacology / Q000627:therapeutic use; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D002121:Calcium Channel Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D009569:Nitric Oxide; D005492:Folic Acid