The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium

Abstract

The direct positive inotropic effects of dopamine and its precursor, levodopa, were measured using isolated, contracting human papillary muscle strips taken from patients during mitral valve replacement. Levodopa did not produce any positive inotropic effect at concentrations up to 3 X 10(-3) M. The positive inotropic effects of dopamine were observed at concentrations above 1 X 10(-5) M with the maximal effect at 3 X 10(-3) M - concentrations higher than those observed in therapy. This inotropic effect was reduced by the beta 1-selective antagonist, 1-practolol (1 X 10(-6) M); the beta 2-selective antagonist, ICI 118,551 HCl (1 X 10(-6) M); the dopamine antagonist, haloperidol (3 X 10(-6) M); the neuronal uptake inhibitor, cocaine (3 X 10(-5) M), but not by the alpha 1-antagonist, prazosin (1 X 10(-7) M). This indicates that dopamine exerts its positive inotropic effects on human heart muscle mainly through release of noradrenaline, together with possible interactions at beta- and dopamine-receptors. The maximal inotropic effect of dopamine was about 50% that of calcium (15 mM, 6.2 +/- 0.7 mN) or ouabain (1 X 10(-7) M, 5.0 +/- 0.8 mN) when measured in the same muscle strips, possibly due to the reduced cardiac noradrenaline content together with the reduced beta-receptor number in congestive heart failure. This concentration of ouabain (1 X 10(-7) M) gave almost maximal inotropy without marked toxicity; when dopamine was then added, only toxicity developed without any further increases in force of contraction. Any haemodynamic benefits of dopamine therapy in optimally digitalis-treated patients are probably due to other cardiovascular effects such as vasodilatation.

Dose-dependent separation of dopaminergic and adrenergic effects of epinine in healthy volunteers

“…Since the increase in plasma noradrenaline induced by dopamine was not affected by bisoprolol, propranolol or domperidone it appears not to be a receptor-mediated one, but rather seems to reflect the indirect (tyramine-like) effect of dopamine. Thus, these data obtained in vivo in humans are in accordance with previously published data obtained in vitro in myocardial preparations of several species, including humans, that the effects of dopamine consist of a direct and indirect (via the release of noradrenaline) component (Deighton et al 1992;Mugelli et al 1977;Brodde et al 1980;Brown et al 1985;Port et al 1990) while that of epinine is largely a direct one (Deighton et al 1992;Brodde et al 1979;English et al 1986;Anderson et al 1992). …”

Modulation of the Negative Inotropic Effect of Haloperidol by Drugs with Positive Inotropic Effects in Isolated Rabbit Heart

“…The dopamine D 2 receptors are involved in the direct positive inotropic effect of dopamine, as dopamine increases [Ca 2+ ] i through actions mediated by dopamine D 2 receptors [37]. Moreover, it has been reported that haloperidol reduces the inotropic effect of dopamine [36,38] and of dopaminergic drugs [39]. In this study, dopamine diminished the negative inotropic effect of haloperidol.…”

“…However, our results showed that the pattern of interference of dopamine with haloperidol was of a noncompetitive pattern. This is because dopamine increases Ca 2+ availability not only by activities on the dopamine receptors but additionally by other mechanisms like activation of adrenergic ß 1 -and ß 2 -receptors and release of norepinephrine [36]. It is noteworthy that norepinephrine and dopamine did not completely antagonize the effect of haloperidol.…”

“…It has been reported that stimulation of the dopaminergic neurons in the ventral tegmental area induces a pressor response [35]. On the other hand, dopamine produces a direct positive inotropic effect at concentrations 10.1 Ìmol/l [36]. The dopamine D 2 receptors are involved in the direct positive inotropic effect of dopamine, as dopamine increases [Ca 2+ ] i through actions mediated by dopamine D 2 receptors [37].…”

Impairment of the cardiac ejection fraction by blocking dopamine D2 receptors induced by long-acting injectable antipsychotic treatment

“…The large number of dopamine receptors in the cerebral vessels influences the cerebral vascularization and the preservation of a normal cerebral blood flow (CBF). Stimulation of DRD2 at the heart level causes an inotropic effect [ 52 ], which ensures efficient contraction of the myocardium, especially in the left ventricle. In this way, a normal EF is maintained which ensures a normal CBF, while maintaining the proper functioning of all brain structures (Figure 7 ).…”