Stimulation of beta-adrenoceptors by dobutamine in the guinea-pig atrium and tracheal chain.

Abstract

Experiments with the dopamine-congener dobutamine were performed on isolated, spontaneously beating right atria as well as on electrically driven left atria of guinea pigs (2 and 3 Hz). Furthermore, its relaxant effect on the tracheal chain was investigated. 1. On right atria dobutamine caused a positive chronotropic effect, the corresponding pD2-value was by 1.75 log units lower than that determined for isoprenaline. The intrinsic activity (isoprenaline=1) was 0.79 for the increase in rate. The pA2-value characterizing the antagonism between metoprolol and dobutamine or isoprenaline for the positive chronotropic effect were comparable indicating that the effects are mediated by the same type of β-adrenoceptor. 2. On the left atrium driven at 2 Hz the pD2-value for the positive inotropic effects of dobutamine and isoprenaline was by 1.82 log units lower for dobutamine than for isoprenaline. The intrinsic activity of dobutamine amounted to 0.62 (isoprenaline=1.0). The pA2-values of metoprolol, on the other hand, did not differ significantly in the presence of either dobutamine or isoprenaline. 3. Since the right atria developed a spontaneous rate of about 3 Hz, left atria were also driven at 3 Hz. The pD2-values of dobutamine under these conditions were 6.05 for the positive chronotropic effect obtained on right atria and 6.07 for the positive inotropic effect obtained on left atria, also the pA2-values determined for metoprolol showed no significant differences. 4. Dobutamine completely relaxed the guinea-pig tracheal chain preparation, its intrinsic activity was identical with that of isoprenaline. The pD2-value amounted to 5.38, that determined for isoprenaline was 7.86. The corresponding pA2-values for metoprolol did not differ from each other: in the presence of dobutamine it amounted to 6.55, while for isoprenaline it was 6.50. 5. By stimulation of cardiac β1-adrenoreceptors dobutamine causes — like isoprenaline — positive inotropic and chronotropic effects of comparable degree. The tracheal β2-adrenoreceptors are also stimulated by dobutamine; the pD2-value for tracheal relaxation was by about 0.69 log units lower than that for cardiostimulation.