Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism

Abstract

Nebivolol, a beta 1 selective adrenergic receptor antagonist with additional properties, is a racemic mixture of (S,R,R,R)- and (R,S,S,S)-enantiomers. We investigated its effects on human forearm vasculature. Blood flow was measured using venous occlusion plethysmography during brachial artery infusion of drugs. Interaction between nebivolol and the L-arginine/nitric oxide pathway was investigated via comparison with carbachol (an endothelium-dependent agonist) and nitroprusside, and by coinfusion of a competitive inhibitor of nitric oxide synthase, NG-monomethyl L-arginine (LNMMA) +/- L-arginine. Nebivolol (354 micrograms/min) increased blood flow by 91 +/- 18% (mean +/- SEM, n = 8, P < .01) whereas an equimolar dose of atenolol had no significant effect. L-NMMA (1 mg/min) inhibited vasodilation to nebivolol (by 65 +/- 10%) and carbachol (by 49 +/- 8%) to a significantly greater extent than it reduced responses to nitroprusside. Inhibition of nebivolol response by L-NMMA was abolished by L-arginine (62 +/- 11% inhibition by L-NMMA, 15 +/- 17% inhibition by L-NMMA with L-arginine, 10 mg/min, n = 8). Vasodilation caused by the (S,R,R,R)- and (R,S,S,S)-enantiomers was similar. We conclude that nebivolol vasodilates human forearm vasculature via the L-arginine/nitric oxide pathway.