NEBIVOLOL VASODILATES HUMAN FOREARM VASCU LATURE - 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 now was measured using venous occlusion plethysmography during b rachial artery infusion of drugs. Interaction between nebivolol and th e L-arginine/nitric oxide pathway was investigated via comparison with carbachol (an endothelium-dependent agonist) and nitroprusside, and b y coinfusion of a competitive inhibitor of nitric oxide synthase, N-G- monomethyl L-arginine (L-NMMA) +/- L-arginine. Nebivolol (354 mu g/min ) increased blood now by 91 +/- 18% (mean +/- SEM, n = 8, P < 0.01) wh ereas an equimolar dose of atenolol had no significant effect. L-NMMA (1 mg/min) inhibited vasodilation to nebivolol (by 65 +/- 10%) and car bachol (by 49 +/- 8%) to a significantly greater extent than it reduce d responses to nitroprusside, Inhibition of nebivolol response by L-NM MA 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). Vasodil ation caused by the (S,R,R,R)- and (R,S,S,S)-enamtiomers was similar. We conclude that nebivolol vasodilates human forearm vasculature via t he L-arginine/nitric oxide pathway.