alexa Pharmacological augmentation of endothelium-derived nitric oxide synthesis.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Bakris GL

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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. SUMMARY: 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. CONCLUSION: 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.
This article was published in J Manag Care Pharm and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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