Ligands at beta2-, beta3-, and the low-affinity state of beta1-adrenoceptors block the alpha1-adrenoceptor-mediated constriction in human pulmonary and rat mesenteric arteries

J Cardiovasc Pharmacol. 2005 Jul;46(1):76-82. doi: 10.1097/01.fjc.0000162775.23139.3e.

Abstract

We examined whether the beta2-adrenoceptor agonists fenoterol and salbutamol, the beta3-adrenoceptor agonists CL 316243 and ZD 2079, and the agonists of the low-affinity state of beta-adrenoceptors, cyanopindolol and CGP 12177 block alpha1-adrenoceptors in that concentration range in which they relax the human pulmonary and rat mesenteric arteries preconstricted with phenylephrine 10 microM and 1 microM, respectively. For quantification of vasodilatation pEC25 values and for the antagonism toward alpha1-adrenoceptors, pA2 values were determined. We found that in the rat mesenteric artery, (1) the pEC25 values of the beta-adrenoceptor ligands resemble their respective pA2 values (difference < or = 0.9 log units), and (2) the order of potencies is the same for both parameters, ie, cyanopindolol approximately fenoterol > CGP 12177 > salbutamol > ZD 2079 > CL 316243. In the human pulmonary artery, (1) the pEC25 values are slightly lower (by 0.6-1.3 log units) than their respective pA2 values, and (2) the rank order of potencies is the same for both parameters. In conclusion, the present study suggests that ligands of beta2-adrenoceptors and of non-beta1-non-beta2-adrenoceptors relax rat and human vessels preconstricted with phenylephrine or norepinephrine mainly through their alpha1-adrenolytic effects. Hence, for the investigation of the role of beta-adrenoceptors in vessels, the constrictor agent should be chosen with great caution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-3 Receptor Antagonists
  • Adrenergic beta-Agonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • In Vitro Techniques
  • Ligands
  • Male
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / physiology
  • Middle Aged
  • Phenylephrine / pharmacology
  • Propanolamines / pharmacology
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, Adrenergic, beta-3 / metabolism
  • Vasoconstriction / drug effects*

Substances

  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-3 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Ligands
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • Phenylephrine
  • CGP 12177