β1-, β2- and atypical β-adrenoceptor-mediated relaxation in rat isolated aorta

Abstract

1. β-adrenoceptor-mediated relaxation was investigated in ring preparations of rat isolated thoracic aorta. Rings were pre-constricted with a sub-maximal concentration of noradrenaline (1 μM) and relaxant responses to cumulative concentrations of β-adrenoceptor agonists obtained. 2. The concentration-response curve (CRC) to isoprenaline was shifted to the right by propranolol (0.3 μM) with a steepening of the slope. Estimation of the magnitude of the shift from EC50 values gave a pA2 of 7.6. Selective β1- and β2-adrenoceptor antagonists, CGP 20712A (0.1 μM) and ICI 118551 (0.1 μM), respectively, produced 4 and 14 fold shifts of the isoprenaline CRC. 3. Atypical β-adrenoceptor agonists also produced concentration-dependent relaxation of aortic rings. The order of potency of the β-adrenoceptor agonists was (-log EC50): isoprenaline (6.25) > cyanopindolol (5.59) > isoprenaline + propranolol (5.11) > CGP 12177A (4.40) > ZD 2079 (4.24) > ZM 215001 (4.07) > BRL 37344 (3.89). Relaxation to CGP 12177A and ZM 215001 was unaffected by propranolol (0.3 μM). 4. SR 59230A (≤ 1 μM) and cyanopindolol (1 μM), β3-adrenoceptor antagonists, had no effect on the isoprenaline (in the presence of propranolol) or CGP 12177A CRCs. Bupranolol and CGP 20712A, at μM concentrations (β4-adrenceptor antagonists), inhibited responses to isoprenaline (in the presence of propranolol) and CGP 12177A. 5. In conclusion, atypical β-adrenoceptors co-exist with β1- and β2-adrenoceptors in rat aorta. Although non-conventional partial agonists and selective β3-adrenoceptor agonist cause relaxation, the vascular atypical β-adrenoceptor does not appear to correspond to the β3-adrenoceptor. There are, however, similarities with the putative β4-adrenoceptor.