FACTORS UNDERLYING THE VARIABLE INOTROPIC EFFECT OF OUABAIN ON ISOLATED RAT ATRIA - CHANGES IN CONTRACTILE FREQUENCY AND ADRENERGIC-MECHANISMS

The effects of concentrations of ouabain on the isometric developed tension (IDT) of isolated left auricles driven at 0·4, 0·8 and 3·3 Hz, were explored. With 0·4 or 0·8 Hz, increasing concentrations of ouabain (3·4 or 6·8 times 10−6; 1·0; 3·4 or 6·8 times 10−6M) elicited a decreasing enhancement of atrial contractile peak tension, whereas with 3·3 Hz the effect was augmented with concentration. Ouabain (3·4 times 10−6 M) enhanced comparably the IDT at all the driving rates, but at higher concentrations the effect varied with the frequency. The positive inotropic action of ouabain at 3·4 times 10−6 M on preparations driven at faster frequencies was antagonized by Sotalol (MJ‐1999) and also after catecholamine depletion by in vivo reserpinization followed by addition of tyramine in vitro. Cocaine or U‐0521 significantly enhanced the positive inotropic effect of ouabain (3·4 times 10−5 M) in atria stimulated at low rates. On the contrary, Sotalol, cocaine, U‐0521 or catecholamine depletion did not alter the positive inotropic influence of ouabain at 3·4 times 10−6 M at any of the frequencies used. It is suggested that ouabain influenced contractile peak tension of rat isolated atria through two mechanisms: one, seen after higher concentrations, which appeared to be associated with adrenergic factors and dependent on the frequency of stimulation; the other, observable with the lower concentrations, which did not appear to have a direct relationship with adrenergic processes and which was independent of the frequency of stimulation. 1979 Royal Pharmaceutical Society of Great Britain