A Positive Influence of Frequency on the Inotropic Response of Isolated Rat Atria to Certain Adrenergic Amines. Effects of Cocaine and U-0521 (3′,4′-Dihydroxy-2-methyl Propiophenone) 1

Abstract

Summary

The effects of several inotropic interventions on the isometric developed tension (IDT) of isolated left rat atrium, electrically driven at several frequencies were investigated. The experimental stimulating procedure allowed the attainment at all the rates tested (25, 50, 100, and 200 per min), similar magnitudes of IDT prior to drug addition. Two types of contractile responses to the inotropic agents at different beating frequencies were found: (1) Norepinephrine and isoproterenol enhanced the IDT less at the slower rates (25 and 50 per min) than at the highest rate (200 per min); (2) phenylephrine and CaCl₂ similarly augmented atrial IDT at all driving rates. The presence of cocaine potentiated the effect of norepinephrine at lower frequencies but not at 200 beats per min; in addition, it did not modify the inotropic influence of isoproterenol at any of the rates explored. U-0521 enhanced the positive inotropism of both norepinephrine and isoproterenol only at low stimulating frequencies. The results suggest that: (a) The dissimilar effects of norepinephrine and isoproterenol at low and high rates could be associated with a different importance of the inactivating processes of these amines at the various frequencies, namely, presynaptic neuronal uptake and metabolization via COMT. Both mechanisms appear to be more important at lower rates and this could be the reason underlying a diminished influence of norepinephrine or isoproterenol over slowly beating atria. (b) The positive influence of frequency over the inotropic effects of norepinephrine and isoproterenol is not due to the magnitude of atrial contractions existing before their addition.