Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery

Naunyn Schmiedebergs Arch Pharmacol. 2005 Jul;372(1):14-23. doi: 10.1007/s00210-005-1082-2. Epub 2005 Aug 26.

Abstract

The aim of this study was to analyze beta-adrenoceptor (beta-AR)-mediated relaxation in rat intralobar pulmonary artery. The relaxant responses of beta-AR agonists were characterized using beta-AR antagonists in prostaglandin F2alpha (PGF2alpha)-precontracted arteries. The role of nitric oxide (NO) and endothelium in beta-AR-mediated relaxation was also investigated. Isoprenaline (a non-selective beta-AR agonist) and salbutamol (a selective beta2-AR agonist) induced vasorelaxation. ICI 118551 (a selective beta2-AR antagonist) antagonized the effect of both isoprenaline and salbutamol (pA2 values of 9.57 and 9.51 respectively). In contrast, atenolol (1 microM) and CGP 20712A (0.1 microM), two beta1-AR antagonists, did not modify the relaxing effect of isoprenaline. The response to isoprenaline obtained in the presence of nadolol (10 microM, a beta1/beta2-AR antagonist) was not further inhibited by SR 59230A (1 microM, a selective beta3-AR antagonist). The non-beta1/beta2-AR agonists studied (BRL 37344, SR 58611A, and CGP 12177A) did not elicit vasorelaxation. Relaxation to isoprenaline and salbutamol was unaffected by L-N(G)-nitro-arginine methyl ester (100 microM, an inhibitor of NO synthase) or after endothelium removal. These results demonstrate the role of beta2-AR in mediating relaxation in rat intralobar pulmonary artery precontracted with PGF2alpha. They indicate that beta2-AR-mediated relaxation in this artery is NO- and endothelium-independent. Furthermore, they do not provide evidence of a relaxant role of either beta1- or beta3-AR in PGF2alpha-precontracted rat intrapulmonary artery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Albuterol / pharmacology
  • Animals
  • Atenolol / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Propanolamines / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / analysis
  • Receptors, Adrenergic, beta-1 / drug effects
  • Receptors, Adrenergic, beta-2 / analysis
  • Receptors, Adrenergic, beta-2 / drug effects
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Receptors, Adrenergic, beta-3 / analysis
  • Receptors, Adrenergic, beta-3 / drug effects
  • Vasodilation* / drug effects

Substances

  • 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Receptors, Adrenergic, beta-3
  • Nitric Oxide
  • ICI 118551
  • Atenolol
  • Nitric Oxide Synthase
  • Isoproterenol
  • Albuterol
  • NG-Nitroarginine Methyl Ester