DEMONSTRATION OF BOTH β1‐ AND β2‐ADRENOCEPTORS MEDIATING RELAXATION OF ISOLATED RING PREPARATIONS OF RAT PULMONARY ARTERY

Abstract

1 Cumulative concentration-response (relaxation) curves to three β-adrenoceptor agonists, fenoterol (β₂-selective), isoprenaline (non-selective) and noradrenaline (β₁-selective) were obtained on isolated ring preparations of rat pulmonary artery contracted with 15 mM KCl. α-Adrenoceptors and neuronal and extraneuronal uptakes were blocked with phenoxybenzamine. The agonist concentration-response curves were reproducible. 2 Responses to each of the three agonists could be blocked by the β-adrenoceptor antagonists atenolol (β₁-selective) or ICI 118,551 (β₂-selective) confirming the presence of β-adrenoceptors. 3 The relative potencies of the agonists were isoprenaline: fenoterol: noradrenaline = 100: 38: 1.4. This indicated that the predominant β-adrenoceptor type was β₂. 4 Schild plots were obtained for atenolol and ICI 118,551 using the three different agonists. For each antagonist the location of the Schild plot varied depending on which agonist was used. This indicated that the β-adrenoceptor population mediating relaxation responses to β-adrenoceptor agonists was not homogeneous. 5 Atenolol was most potent when noradrenaline was the agonist and ICI 118,551 was most potent when fenoterol was the agonist. 6 It is concluded that isolated pulmonary artery ring preparations of the rat contain a mixed population of β₁- and β₂-adrenoceptors both mediating relaxation.