RT Journal Article
SR Electronic
T1 Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1067
OP 1071
VO 274
IS 3
A1 J R Cockcroft
A1 P J Chowienczyk
A1 S E Brett
A1 C P Chen
A1 A G Dupont
A1 L Van Nueten
A1 S J Wooding
A1 J M Ritter
YR 1995
UL http://jpet.aspetjournals.org/content/274/3/1067.abstract
AB 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.