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. 1994 Sep;38(3):199–204. doi: 10.1111/j.1365-2125.1994.tb04342.x

Nitric oxide mediated venodilator effects of nebivolol.

A J Bowman 1, C P Chen 1, G A Ford 1
PMCID: PMC1364790  PMID: 7826820

Abstract

1. Nebivolol, a selective beta 1-adrenoceptor antagonist with antihypertensive effects, has haemodynamic effects suggestive of a direct vasodilator action. 2. The dorsal hand vein technique was used to determine whether nebivolol has venodilator action in vivo in man. 3. Nebivolol and atenolol were infused into the phenylephrine preconstricted superficial hand veins of 11 healthy male volunteers. In separate studies L-NMMA (0.1 microgram min-1) was pre- and co-infused with nebivolol to determine whether nitric oxide (NO) mediated mechanisms were present. Further studies with prostaglandin F2 alpha (PGF2 alpha) preconstriction were performed to exclude an alpha-adrenergic antagonistic effect of nebivolol. Effects of L-NMMA infusion on nitroglycerin venodilation were also determined. 4. Nebivolol produced a dose dependent venodilation, (72 +/- 18% maximum), whereas atenolol produced no significant venodilation. At doses of nebivolol producing plasma concentrations comparable with plasma levels achieved after standard oral dosing (10(-13)-10(-12) mol min-1) small (14 +/- 6% and 23 +/- 8%) but significant (P < 0.05) venodilation was observed. 5. The venodilator response to nebivolol was significantly reduced by infusion of L-NMMA (maximum dilation 18% vs 72%, P < 0.01). Venodilator responses to nitroglycerin were unaffected by L-NMMA infusion. A venodilator effect to nebivolol was also seen following preconstriction with PgF2 alpha (40 +/- 20% maximum). 6. Nebivolol has nitric oxide mediated, venodilator effects in man.

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Selected References

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  1. Aellig W. H. A new technique for recording compliance of human hand veins. Br J Clin Pharmacol. 1981 Mar;11(3):237–243. doi: 10.1111/j.1365-2125.1981.tb00527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Araki H., Itoh M., Nishi K. Effects of nipradilol on the microvascular tone of rat mesentery: comparison with other beta-blockers and vasodilators. Arch Int Pharmacodyn Ther. 1992 Jul-Aug;318:47–54. [PubMed] [Google Scholar]
  3. Bashir Y., McKenna W. J., Camm A. J. Beta blockers and the failing heart: is it time for a U-turn? Br Heart J. 1993 Jul;70(1):8–12. doi: 10.1136/hrt.70.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bossaller C., Habib G. B., Yamamoto H., Williams C., Wells S., Henry P. D. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987 Jan;79(1):170–174. doi: 10.1172/JCI112779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Calver A., Collier J., Moncada S., Vallance P. Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal. J Hypertens. 1992 Sep;10(9):1025–1031. [PubMed] [Google Scholar]
  6. Ford G. A., Hoffman B. B., Vestal R. E., Blaschke T. F. Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man. Br J Clin Pharmacol. 1992 Jan;33(1):83–87. doi: 10.1111/j.1365-2125.1992.tb04004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gao Y. S., Nagao T., Bond R. A., Janssens W. J., Vanhoutte P. M. Nebivolol induces endothelium-dependent relaxations of canine coronary arteries. J Cardiovasc Pharmacol. 1991 Jun;17(6):964–969. doi: 10.1097/00005344-199106000-00016. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Kemp P. A., Bennett T. Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats. Br J Pharmacol. 1991 Jul;103(3):1725–1732. doi: 10.1111/j.1476-5381.1991.tb09854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graves J., Poston L. Beta-adrenoceptor agonist mediated relaxation of rat isolated resistance arteries: a role for the endothelium and nitric oxide. Br J Pharmacol. 1993 Mar;108(3):631–637. doi: 10.1111/j.1476-5381.1993.tb12853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Janczewski P., Boulanger C., Iqbal A., Vanhoutte P. M. Endothelium-dependent effects of carteolol. J Pharmacol Exp Ther. 1988 Nov;247(2):590–595. [PubMed] [Google Scholar]
  11. Janssens W. J., Van de Water A., Xhonneux R., Reneman R. S., Van Nueten J. M., Janssen P. A. Nebivolol is devoid of intrinsic sympathomimetic activity. Eur J Pharmacol. 1989 Jan 2;159(1):89–95. doi: 10.1016/0014-2999(89)90047-2. [DOI] [PubMed] [Google Scholar]
  12. Johnson R. A., Freeman R. H. Sustained hypertension in the rat induced by chronic blockade of nitric oxide production. Am J Hypertens. 1992 Dec;5(12 Pt 1):919–922. doi: 10.1093/ajh/5.12.919. [DOI] [PubMed] [Google Scholar]
  13. Kou K., Suzuki H. The effects of 3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitroxy-2H-1-benzopyran (K-351) and its denitrated derivative on smooth muscle cells of the dog coronary artery. Br J Pharmacol. 1983 May;79(1):285–295. doi: 10.1111/j.1476-5381.1983.tb10523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McTavish D., Campoli-Richards D., Sorkin E. M. Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs. 1993 Feb;45(2):232–258. doi: 10.2165/00003495-199345020-00006. [DOI] [PubMed] [Google Scholar]
  15. Moncada S., Rees D. D., Schulz R., Palmer R. M. Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2166–2170. doi: 10.1073/pnas.88.6.2166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mostaghim R., Maddox Y. T., Ramwell P. W. Endothelial potentiation of relaxation response to beta adrenoceptor blocking agents. J Pharmacol Exp Ther. 1986 Dec;239(3):797–801. [PubMed] [Google Scholar]
  17. Ohira A., Wada Y., Fujii M., Nakamura M., Kasuya Y., Hamada Y., Shigenobu K. Effects of nipradilol (K-351) on alpha-adrenoceptor mediated responses in various isolated tissues. Arch Int Pharmacodyn Ther. 1985 Nov;278(1):61–71. [PubMed] [Google Scholar]
  18. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  19. Rees D. D., Palmer R. M., Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989 May;86(9):3375–3378. doi: 10.1073/pnas.86.9.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schneider J., Fruh C., Wilffert B., Peters T. Effects of the selective beta 1-adrenoceptor antagonist, nebivolol, on cardiovascular parameters in the pithed normotensive rat. Pharmacology. 1990;40(1):33–41. doi: 10.1159/000138636. [DOI] [PubMed] [Google Scholar]
  21. Schwartzkopff B., Motz W., Knauer S., Frenzel H., Strauer B. E. Morphometric investigation of intramyocardial arterioles in right septal endomyocardial biopsy of patients with arterial hypertension and left ventricular hypertrophy. J Cardiovasc Pharmacol. 1992;20 (Suppl 1):S12–S17. [PubMed] [Google Scholar]
  22. Schwartzkopff B., Motz W., Knauer S., Frenzel H., Strauer B. E. Morphometric investigation of intramyocardial arterioles in right septal endomyocardial biopsy of patients with arterial hypertension and left ventricular hypertrophy. J Cardiovasc Pharmacol. 1992;20 (Suppl 1):S12–S17. [PubMed] [Google Scholar]
  23. Vallance P., Collier J., Moncada S. Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo. Cardiovasc Res. 1989 Dec;23(12):1053–1057. doi: 10.1093/cvr/23.12.1053. [DOI] [PubMed] [Google Scholar]
  24. Vallance P., Collier J., Moncada S. Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo. Cardiovasc Res. 1989 Dec;23(12):1053–1057. doi: 10.1093/cvr/23.12.1053. [DOI] [PubMed] [Google Scholar]
  25. Van de Water A., Janssens W., Van Neuten J., Xhonneux R., De Cree J., Verhaegen H., Reneman R. S., Janssen P. A. Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. J Cardiovasc Pharmacol. 1988 May;11(5):552–563. doi: 10.1097/00005344-198805000-00007. [DOI] [PubMed] [Google Scholar]

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