NEBIVOLOL VASODILATES HUMAN FOREARM VASCULATURE - EVIDENCE FOR AN L-ARGININE NO-DEPENDENT MECHANISM/

Nebivolol, a beta(1) selective adrenergic receptor antagonist with add itional properties, is a racemic mixture of (S,R,R,R)- and (R,S,S,S)-e nantiomers. 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 t he L-arginine/nitric oxide pathway was investigated via comparison wit h carbachol (an endothelium-dependent agonist) and nitroprusside, and by coinfusion of a competitive inhibitor of nitric oxide synthase, N-G -monomethyl L-arginine (L-NMMA) +/- L-arginine. Nebivolol (354 mu g/mi n) increased blood flow by 91 +/- 18% (mean +/- SEM, n = 8, P < .01) w hereas an equimolar dose of atenolol had no significant effect. L-NMMA (1 mg/min) inhibited vasodilation to nebivolol (by 65 +/- 10%) and ca rbachol (by 49 +/- 8%) to a significantly greater extent than it reduc ed responses to nitroprusside. Inhibition of nebivolol response by L-N MMA 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). Vasodi lation 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.