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 mumol/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 mumol/l and 3.3 nmol/l, respectively. In the presence of the alpha-adrenoceptor blocking agent phentolamine (1 mumol/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 mumol/l. The effects of the catecholamines noradrenaline and adrenaline on force of contraction remained unchanged in the presence of phentolamine (1 mumol/l) or prazosin (1 mumol/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 mumol/l). 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Jahnel
U
U
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany.
Jakob
H
H
Nawrath
H
H
D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013268:Stimulation, Chemical
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D007545:Isoproterenol; D009638:Norepinephrine