Functional alpha-adrenoceptors in human atrial preparations in the presence of beta-receptor blockade

Inotropic effects via cardiac alpha-adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 degrees C) from patients treated with beta-blockers for months prior to open heart surgery. Marked alpha-mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence of beta-blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of approximately 10(-6) M propranolol the maximal effects as well as the potencies (pD2-values) for A and NA were not significantly different while higher than for PHE. The alpha 1-blocker, prazosin (10(-6) M), markedly reduced the pD2-values but not the intrinsic activities (alpha-values) for A, NA and PHE in the beta-blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non-specific, cardiodepressant effects. Other agonists with alpha-effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions. The results show alpha 1-type of adrenoceptor-induced inotropic effects for A, NA and PHE during beta-blockade in human auricular strips, indicating that cardiac alpha 1-receptors may have clinical importance by increasing the inotropy of the human myocardium treated with beta-blocking agents.