THE EFFECTS OF AMOSULALOL, A NOVEL COMBINED α‐ AND β‐ADRENORECEPTOR ANTAGONIST, ON THE RAT ISOLATED RIGHT VENTRICLE AND AORTA

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Abstract
The effect of amosulalol on the accumulation of radioactivity from [3H]-noradrenaline and on the subsequent spontaneous and nerve stimulation-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effect of amosulalol on the contractions of the electrically-driven directly muscle stimulated rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5-hydroxytryptamine are reported. Amosulalol at 10-6 M did not prevent the accumulation of radioactivity from a solution containing [3H]-noradrenaline. The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]-noradrenaline, was increased by amosulalol at 10-6 M by a cocaine- and idazoxan-insensitive mechanism. The nerve stimulation-evoked outflow of radioactivity was increased by amosulalol (10-6 M), cocaine (10-5 M) and idazoxan (10-7 M). The ability of amosulalol to increase nerve-evoked outflow was maintained in the presence of cocaine but prevented by pretreatment with idazoxan. This suggests that amusulalol is an .alpha.2-adrenoreceptor antagonist. The contractile response of the electrically-driven directly muscle stimulated right ventricle to isoprenaline were inhibited by amosulalol at 10-7 and 10-6 M with apparent pA2 values of 7.5 and 8.1, respectively. It is suggested that amosulalol at 10-6 M may have an action additional to .beta.1-adrenoreceptor antagonism on the right ventricle. The contractile responses of the rat aorta to phenylephrine were inhibited by amosulalol at 10-7 and 10-6 M with a pA2 of 8.6 which was independent of concentration. Amosulalol also reduced the magnitude of the maximal responses of the aorta to 5-hydroxytryptamine.