Interaction of selected vasodilating beta-blockers with adrenergic receptors in human cardiovascular tissues

J Cardiovasc Pharmacol. 1989 Jul;14(1):114-20. doi: 10.1097/00005344-198907000-00020.

Abstract

beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Aged
  • Cardiovascular System / drug effects
  • Cardiovascular System / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Mammary Arteries / drug effects
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Norepinephrine / metabolism
  • Pindolol / metabolism
  • Prazosin / metabolism
  • Proteins / metabolism
  • Receptors, Adrenergic / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Adrenergic beta-Antagonists
  • Iodine Radioisotopes
  • Proteins
  • Receptors, Adrenergic
  • Vasodilator Agents
  • Pindolol
  • Norepinephrine
  • Prazosin