Nitric oxide mechanisms of nebivolol.
beta-blockers are among the most widely used drugs in the prevention and treatment of cardiovascular disease, although they are associated with increased peripheral resistance. Third-generation beta-blockers avoid this adverse effect by inducing vasodilation through different mechanisms. In particular, nebivolol, a highly selective blocker of beta(1)-adrenergic receptors, is the only beta-blocker known to induce vascular production of nitric oxide, the main endothelial vasodilator. The specific mechanism of nebivolol is particularly relevant in hypertension, where nitric oxide dysfunction occurs. Indeed, nebivolol is able to reverse endothelial dysfunction. Nebivolol induces nitric oxide production via activation of beta(3)-adrenergic receptors, which can explain the good metabolic profile observed after treatment with this drug. Moreover, nebivolol can also stimulate the beta(3)-adrenergic receptor-mediated production of nitric oxide in the heart, and this stimulation can result in a greater protection against heart failure. In conclusion, nebivolol has a unique profile among antihypertensive drugs, adding to a very high selectivity against beta(1) adrenergic receptors, and an agonist action on beta(3) receptors and nitric oxide (NO), which has led to clinically significant improvements in hypertensive patients.
Maffei
Angelo
A
Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli (IS), Italy.
Lembo
Giuseppe
G
D058671:Adrenergic beta-1 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001578:Benzopyrans / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use
D058671:Adrenergic beta-1 Receptor Antagonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide