Interactions of ouabain and noradrenaline in isolated rabbit's atria

Abstract

1. The present study was made using sympathetic nerve-atria preparations, conventional atrial preparations and left atria isolated from raibbits in order that interactions of ouabain and noradrenaline on the transmemibrane potential of S-A nodal pacemaker fibres, the pacemaker rate and the contractile force of the left atrium could be investigated. 2. In pacemaker action potentials, the maximal diastolic potential was decreased, the early repolarization was accelerated and the late repolarization was slowed by toxic concentrations of ouabain. Oscillating potentials of the diastolic pacemaker membrane were produced. 3. Stimulation of the postganglionic sympathetic nerve caused an increase in the slope of diastolic depolarization, resulting in an acceleration of the pacemaker rate. In the presence of ouabain, the pacemaker action potential configuration was significantly altered 'by nerve stimulation in preparations which showed ouabain-induced bradycardia, but the potential configuration was not changed by nerve stimulation in preparations which showed ouabaininduced tachycardia. Cardiac noradrenaline altered the ion permeability of the cardiac pacemaker membrane during diastole, but it had no effect during systole. Sympathetic nerve stimulation transiently corrected the overshoot and the repolarization of atrial action potentials altered by toxic concentrations of oualbain. 4. The positive chronotropic effect of sympathetic nerve stimulation was not affected by either therapeutic or toxic concentrations of oualbain. Ouabain shifted the concentration-chronotropic response curve for exogenous noradrenaline to the left, but did not shift the curve for tyramine. 5. Relationship between the developed tension and the rate of contraction was altered differently by oualbain and by noradrenaline. The positive inotropic effect of noradrenaline was not significantly altered by therapeutic concentrations of ouafbain but it was inhibited by toxic concentrations.In earlier reports (McEwen, 1956;Toda & West, 1966) it has been shown that ouabain causes a potentiation of the negative chronotropic response of isolated mammalian hearts to vagal stimulation and to acetylcholine and an alteration in the membrane effect of cardiac acetylcholine. However, little quantitative-data are available on the interaction of ouabain and noradrenaline on the pacemaker membrane, on the S-A nodal rate and on the contractile force of isolated hearts.Ouabain in toxic concentrations causes measura(ble changes in the transmemibrane potential of S-A nodal pacemaker fibres (Toda & West, 1966), which are postulated

Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline

“…Pharmacological and other methods for increasing atrial contractile tension can be divided into two groups: (a) an elevation in [Ca++]o, noradrenaline and coupled pacing which shift the tension-rate curves upward, and (b) a reduction of [Na+]o, a reduction of [K+]o and toxic concentrations of ouabain (Toda, 1969a) which produce an enhancement of the contractile tension only at low driving rates. Baker & Baker (1955) demonstrated similarities between the actions of adrenaline and Ca++ on the electrical and mechanical events of frog'hearts.…”

“…Therefore, coupled pacing is thought of as a technique of electrodigitalization (Sarnoff, Gilmore, Daggett, Mansfield, McDonald & Weisfeldt, 1965). However, alterations in the tension-rate curve induced by coupled pacing and oua'bain (Toda, 1969a) …”

“…produced a measurable decrease in both of R, and R2 (Toda, unpublished data Table 2. Data relating to ouabain were obtained from previous experiments (Toda, 1969a), in which the same experimental conditions were used. Trends of increasing R1 and R2 were observed in preparations exposed to noradrenaline, low [K+] (Fig.…”

“…The present study was undertaken to investigate alterations in the contractile tensiondriving rate relationship caused by varying extracellular concentrations of cations, by noradrenaline and by coupled pacing, as compared with those induced by ouabain (Toda, 1969a).…”

“…It has been demonstrated that the positive inotropic effect of sympathomimetic amines is reduced by metabolic inhibitors (Dhalla & Braxton, 1968) and ouabain (Toda, 1969a). It is suggested by the former investigators that some energydependent process is involved in an increase in intracellular concentrations of Ca++ available for contraction following stimulation of adrenergic receptors.…”