Systemic hemodynamic effects of dopamine, [formula omitted] and the (+)- and (−)-enantiomers of dobutamine in anesthetized normotensive rats

Abstract

The hemodynamic effects of dopamine, (±)- dobutamine (racemic mixture), and the (+)- and (−)-enantiomers of dobutamine were evaluated in anesthetized normotensive rats. Dopamine and (±)- dobutamine produced hemodynamic effects in anesthetized rat that were qualitatively similar to those reported for these compounds in man. The increase in cardiac output produced by dopamine and (±)- dobutamine was due mainly to an increase in stroke volume, with heart rate being only minimally affected. Dopamine produced a large increase in mean arterial pressure and slightly increased total peripheral vascular resistance, whereas (±)- dobutamine only modestly increased blood pressure and significantly produced total peripheral resistance. The (−)-enantiomer of dobutamine, which possesses mainly α 1- adrenoceptor agonist activity, produced marked increases in cardiac output, stroke volume, total peripheral resistance and mean arterial pressure, but did not significantly increase heart rate. In contrast, (+)-dobutamine, which possesses predominantly β 1 - and β 2- adrenoceptor agonist activity, elicited only a modest increase in cardiac output which was due entirely to increased heart rate since stroke volume was not increased. Total peripheral vascular resistance and mean arterial blood pressure were both reduced by (+)-dobutamine, characteristics of a β-adrenoceptor agonist. The increase in cardiac output and blood pressure produced by (±)- dobutamine , but not the positive chronotropic effect, were significantly inhibited by α 1- adrenoceptor blockade with prazosin. Based on the marked increase in cardiac output and stroke volume elicited by the (−)-enantiomer of dobutamine ( α 1- adrenoceptor agonist), and the ability of prazosin to antagonize the increase in cardiac output and stroke volume produced by (±)- dobutamine , we conclude that the effects of (±)- dobutamine on cardiac performance are mediated, at least in part, by α 1- adrenoceptors possibly residing in the myocardium and mediating a positive inotropic response.