Effects of 1-(4-nitrophenyl)-2-isopropylaminoethanol (INPEA) and propranolol and their dextro-isomers on hemodynamic and metabolic responses to isoproterenol in dogs

Abstract

The effects of dl-propranolol, D-(-)-(4-nitrophenyl)-2-isopropylaminoethanol (INPEA) and L-(+)-INPEA on the hemodynamic and metabolic responses to isoproterenol were investigated in dogs anesthetized with pentobarbital. Isoproterenol (200 micrograms/kg i.p.) was injected 15 min after an i.v. injection of propranolol or INPEA, or their dextro-isomers. Isoproterenol increased heart rate, myocardial contractile force (determined by a strain gauge arch), blood glucose, blood lactate and plasma free fatty acids, and decreased diastolic blood pressure. dl-Propranolol (1 or 3 mg/kg) or D-(-)-INPEA (5 or 15 mg/kg) inhibited all the responses to isoproterenol. d-Propranolol (1 or 3 mg/kg) did not inhibit the isoproterenol-induced responses of heart rate, myocardial contractile force and plasma free fatty acids, but it inhibited the isoproterenol-induced responses of diastolic blood pressure, blood glucose and blood lactate, although the inhibition was small. Similar results were obtained by L-(+)-INPEA; L-(+)-INPEA (5 or 15 mg/kg) did not inhibit the isoproterenol-induced responses of heart rate, myocardial contractile force and plasma free fatty acids, but it inhibited the isoproterenol-induced responses of diastolic blood pressure, blood glucose and blood lactate, although the degree of inhibition was small. These results indicate that dextro-isomers of propranolol and INPEA may have a weak beta-2 adrenoceptor antagonistic action.