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)

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Abstract
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/min), similar magnitudes of IDT prior to drug addition. Two types of contractile responses to the inotropic agents at different beating frequencies were found: norepinephrine [NE] and isoproterenol enhanced the IDT less at the slower rates (25 and 50/min) than at the highest rate (200/min); phenylephrine and CaCl2 similarly augmented atrial IDT at all driving rates. The presence of cocaine potentiated the effect of NE at lower frequencies but not at 200 beats/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 NE and isoproterenol only at low stimulating fequencies. The dissimilar effects of NE 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, i.e., presynaptic neuronal uptake and metabolization via COMT [catechol-O-methyl transferase]. Both mechanisms appear to be more important at lower rates and this could be the reason underlying a diminished influence of NE or isoproterenol over slowly beating atria. The positive influence of frequency over the inotropic effects of NE and isoproterenol is not due to the magnitude of atrial contractions existing before their addition.