Mechanism of the hypotensive effect of a new beta-adrenergic blocking drug, arotinolol (S-596) in anesthetized rabbits.

The mechanism of the hypotensive effect of arotinolol (dl-2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'-th ienyl) thiazole hydrochloride, S-596), a new beta-adrenergic blocking drug with a weak alpha-adrenergic blocking activity, was studied in anesthetized rabbits. Intravenously administered arotinolol produced hypotension at doses above 3 micrograms/kg. Postganglionic renal nerve impulses (RNI) were effect-dependently at doses of 3 and 30 micrograms/kg but augmented after 300 micrograms/kg of arotinolol. The effects of the lower doses of arotinolol were similar to those of clonidine or propranolol, while the effects of the higher doses were similar to those of nitroprusside or phentolamine. The regression line representing the relation between the per cent change of the resting blood pressure and that of the numbers of RNI produced by the lower doses of arotinolol coincided with that of propranolol. Arotinolol blocked the pressor response to phenylephrine but not that to noradrenaline. Administration of arotinolol via the carotid artery produced a hypotension and a concomitant decrease of the numbers of RNI at doses of 3 to 30 micrograms/kg. The above results suggest that the hypotension produced by lower doses of arotinolol was attributable to a decreased sympathetic nervous activity, as is the case with propranolol, while the hypotension by higher doses was peripheral in origin, occurring as a consequence of the blocking effect on the alpha 1-adrenoceptor.