Exploring vascular benefits of endothelium-derived nitric oxide.
Although the regulation of arterial blood flow has been a subject of intensive medical research, the precise circulatory mechanisms involved are still not fully understood. It has been increasingly recognized that the endothelium plays a vital role in regulating vascular tone, structure, and function. A seminal discovery was made with the identification of endothelium-derived relaxing factor, a key mediator of vasodilation, which was later identified as nitric oxide (NO). Nitric oxide is synthesized from the amino acid L-arginine in the endothelium. Decreased bioavailability of NO is associated with arterial stiffness, hypertension, atherosclerosis, and cardiovascular disease (CVD). Nebivolol is a novel beta-blocker that is highly selective for beta1-adrenergic receptors. Nebivolol also causes vasodilation through a mechanism involving endothelium-derived NO. In clinical studies in hypertensive subjects, nebivolol significantly improves vasodilator responses to endothelium-dependent agonists such as acetylcholine. In addition, nebivolol significantly reduces pulse wave velocity (PWV), a measure of arterial stiffness, whereas the beta-blocker atenolol has no effect on PWV. Because endothelial dysfunction and arterial stiffness play an integral part in the early atherosclerotic process and are associated with poor outcomes and increased mortality, independent of blood pressure, the ability of nebivolol to enhance release of endothelium-derived NO may have significant clinical implications for the use of this agent in the treatment of hypertension and CVD.
Cockcroft
John R
JR
Department of Cardiology, Wales Heart Research Institute, Cardiff University, Cardiff, United Kingdom. usher@cardiff.ac.uk
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000503:physiopathology; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology; D004548:Elasticity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005542:Forearm / Q000098:blood supply; D006801:Humans; D000068577:Nebivolol; D009569:Nitric Oxide / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine