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

J. R. Cockcroft, P. J. Chowienczyk, S. E. Brett, C. P H Chen, A. G. Dupont, L. Van Nueten, S. J. Wooding, J. M. Ritter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

358 Citations (Scopus)

Abstract

Nebivolol, a β1 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 (L-NMMA) ± L- arginine. Nebivolol (354 μg/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.

Original languageEnglish
Pages (from-to)1067-1071
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume274
Issue number3
Publication statusPublished - 1995
Externally publishedYes

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