Ritter, James M., Ferro, Albert, and Chowienczyk, Philip J.
European Journal of Clinical Pharmacology; Jan2006 Supplement, Vol. 62, p109-113, 5p, 4 Graphs
ADRENERGIC receptors, NITRIC oxide, VASODILATION, THERAPEUTICS, VASCULAR endothelium, and PROTEIN kinases
This commentary reviews recent evidence that implicates nitric oxide (NO) as a mediator of β2-adrenoceptor (β2-AR)-initiated vasodilatation. Emphasis is placed on the following: 1) in vivo studies that demonstrate potential physiological importance, 2) mechanistic studies performed in vitro in human umbilical vein endothelial cells (HUVEC), 3) effects of β2 agonists on arterial pulse wave reflection, and 4) therapeutic opportunities offered by the combination of β2 agonist action with selective β1 antagonism. Vascular β2-AR-initiated mechanisms provide a physiologically important control mechanism during exercise. Activation of β2-AR in HUVEC leads to vasodilatation that is partly NO-mediated via activation of protein kinase A (PKA) and of phosphatidylinositol-3 kinase (PI3K)/Akt pathways, leading to serine phosphorylation of the endothelial NO synthase (eNOS). In vivo, β2-AR activation limits the rise in blood pressure during exercise and reduces arterial pulse wave reflection. Nebivolol is a selective β1-AR antagonist with vasodilator actions operating through these pathways, offering novel therapeutic opportunities. [ABSTRACT FROM AUTHOR]