title: Pharmacological augmentation of endothelium-derived nitric oxide synthesis.
abstract: BACKGROUND
  The sympathetic nervous system has a unique role in endothelial function, and beta-receptors are a key part of sympathetic nervous system function.
  
  
  OBJECTIVE
  To elucidate the pharmacological augmentation of endotheliumderived nitric oxide synthesis.
  
  
  CONCLUSIONS
  Beta-blockers have been commercially available since the 1960s. Stimulating beta-receptors causes dilatation whereas blocking betareceptors, as traditional beta-blockers do, cause vasoconstriction. However, beta-blockers are hypotensives. This effect probably occurs because they inhibit renin in the kidney and juxtaglomerular apparatus, especially at high doses. They also have some central effects because of central inhibition of the sympathetic nervous system that also lowers blood pressure. In addition, evidence suggests that beta-blockers work at the vascular biology level to produce nitric oxide release. Beta-blockers differ in terms of their betareceptor selectivity, intrinsic sympathomimetic activity, and benefit/risk in diabetes and insulin sensitivity. Nebivolol, the newest of the beta-blockers, is long acting and the most cardioselective beta1-blocker currently available. Nebivolol-induced endothelium- dependent vasodilation associated with activation of the L-arginine/ nitric oxide pathway may confer benefits to patients. The risk for diabetes is lower, the metabolic effects are lower, and people with diabetes who have clear nitric oxide dysfunction may have particular benefits from this agent.
  
  
  CONCLUSIONS
  Third-generation beta-blockers, such as labetolol, carvedilol, bucindolol, and nebivolol, vasodilate by different mechanisms, behaving differently than traditional beta blockers and offering different benefits.
authors.forename: George L
authors.initials: GL
authors.lastname: Bakris
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D004727:Endothelium / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000068577:Nebivolol; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D013564:Sympathetic Nervous System; D014481:United States
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D019001:Nitric Oxide Synthase