Effects of (+)- and (-)-Amosulalol on the Rat Isolated Right Ventricle

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Abstract
The effects of (+)- and (-)-amosulalol on the spontaneous and nerve stimulation-evoked outflow of radioactivity following loading of the rat right ventricle with [3H]noradrenaline and on the contractions evoked either by nerve stimulation or by isoprenaline are reported. The spontaneous outflow of radioactivity was increased by (+)- and (-)-amosulalol at 10-5 M by a cocaine- and idazoxan-insensitive mechanism. (+)-Amosulalol at 10-5 M and (-)-amosulalol at 10-6-10-5 M increased the nerve-evoked outflow of radioactivity. The ability of (+)-amosulalol to increase outflow was reduced by cocaine and idazoxan, whereas the ability of (-)-amosulalol to increase outflow was unaltered by cocaine but abolished by idazoxan pretreatment. This suggests that (-)-amosulalol but not (+)- but not (-)-amosulalol, at 10-6 M is an .alpha.2-adrenoceptor antagonist and that (+)- but not (-)-amosulalol, at 10-5 M, inhibits the neuronal uptake process for noradrenaline. (-)-Amosulalol was a more potent inhibitor of the contractile responses evoked by nerve stimulation than (+)-amosulalol. The contractile responses of the electrically driven direct muscle stimulated right ventricle to isoprenaline were inhibited by (+)-amosulalol at 10-6 M and (-)-amosulalol at 3 .times. 10-8-10-6 M. (-)-Amosulalol (pA2 = 7.9) was 100 times more potent than (+)-amosulalol (pA2 = 5.9) as a .beta.1-adrenoceptor antagonist. In addition, the maximal responses to isoprenaline were reduced by the higher concentrations of (-)-amosulalol tested (10-7-10-6 M). It is suggested that, in addition to being a competitive antagonist at .beta.1-adrenoceptors, (-)-amosulalol may have membrane-stabilizing activity.