The effects of amosulalol, a novel combined alpha- and beta-adrenoreceptor antagonist, on the rat isolated right ventricle and aorta.
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.
Hughes
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Doggrell
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007545:Isoproterenol; D009638:Norepinephrine; D010656:Phenylephrine; D012701:Serotonin; C032473:amosulalol; D000096926:Benzenesulfonamides