ELECTROPHYSIOLOGIC AND INOTROPIC EFFECTS OF ALPHA-ADRENOCEPTOR STIMULATION IN HUMAN ISOLATED ATRIAL HEART-MUSCLE

The effects of alpha-adrenoceptor stimulation on force of contraction were investigated in human atrial heart muscle and compared with those of beta-adrenoceptor stimulation. The maximal positive inotropic effect produced by stimulation of alpha-adrenoceptors with phenylephrine (in the presence of atenolol 10-mu-mol/l) was significantly smaller than that seen in response to beta-adrenoceptor stimulation with isoprenaline. The maximal effect of phenylephrine (25 % of the maximal effect of isoprenaline) required far higher concentrations (1 mmol/l) than isoprenaline (100 nmol/l); the EC50 values amounted to 33.1-mu-mol/l and 3.3 nmol/l, respectively. In the presence of the alpha-adrenoceptor blocking agent phentolamine (1-mu-mol/l), the concentration-response curve of phenylephrine was displaced to higher concentrations of the agonist; under these conditions, the EC50 value amounted to 52.5-mu-mol/l. The effects of the catecholamines noradrenaline and adrenaline on force of contraction remained unchanged in the presence of phentolamine (1-mu-mol/l) or prazosin (1-mu-mol/l). The positive inotropic effect of phenylephrine (1 mmol/l) was associated with a slight decrease in action potential duration; the effects on action potential were completely blocked in the presence of phentolamine (1-mu-mol/1). These findings support the view that selective stimulation of alpha-adrenoceptors may mediate a small but detectable positive inotropic effect in human atrial tissue under in vitro conditions. The requirement of high concentrations of alpha-adrenoceptor agonists and the lack of effects of the endogenous catecholamines adrenaline and noradrenaline on alpha-adrenoceptors (in concentrations which fully elicit the beta-adrenoceptors-mediated response) do not provide a basis for a functional role of alpha-adrenoceptor-mediated effects under in vivo conditions. It is more likely that adrenaline- or noradrenaline-mediated changes in the force of contraction in the human atrium are virtually exclusively due to the stimulation of beta-adrenoceptors.