TY - JOUR
T1 - Nebivolol vasodilates human forearm vasculature
T2 - Evidence for an L- arginine/NO-dependent mechanism
AU - Cockcroft, J. R.
AU - Chowienczyk, P. J.
AU - Brett, S. E.
AU - Chen, C. P H
AU - Dupont, A. G.
AU - Van Nueten, L.
AU - Wooding, S. J.
AU - Ritter, J. M.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0029129670&partnerID=8YFLogxK
M3 - Article
C2 - 7562470
AN - SCOPUS:0029129670
SN - 0022-3565
VL - 274
SP - 1067
EP - 1071
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -