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

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Abstract
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. 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. 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). 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. 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. British Journal of Pharmacology (2000) 129, 637–644; doi:10.1038/sj.bjp.0703091