Positive inotropic response to alpha-adrenergic stimulation in an electrically driven rat left atrium: the role of extracellular calcium.
We studied the positive inotropic response induced by alpha-adrenergic receptor stimulation in an electrically driven rat left atrium. alpha-Adrenergic stimulation resulted in a prolonged positive inotropic response that reached its maximum within 5-7 min. The kinetics of the onset of the positive inotropic response were different for pure alpha-adrenergic, pure beta-adrenergic, and mixed adrenergic stimulation. The positive inotropic responses to alpha- and beta-adrenergic agonists were not additive. The relative inotropic response to alpha-adrenergic stimulation decreased when external calcium concentration was increased and disappeared when external calcium concentration was raised to 7.0 mM. The divalent cation ionophore A23187 (1 microM) produced a threefold increase of the contractility of the atrial preparation at 1.0 mM extracellular calcium, and no further alpha-adrenergic response was observed in its presence. Calcium channel antagonists verapamil and nifedipine markedly inhibited the response to alpha-adrenergic stimulation, with little effect on the beta-adrenergic stimulation, at a calcium concentration of 0.5 mM. The inhibitory effect of calcium channel antagonists could be fully reversed by increasing the extracellular calcium concentration. Our data suggest that the alpha-adrenergic contractile response in the rat atrium involves the mobilization of extracellular calcium through verapamil-sensitive calcium channels in a mechanism different from that for the beta-adrenergic response.
G
G
Shavit
S
S
Gitter
Y
Y
Barak
B A
BA
Vidne
Y
Y
Oron
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D000001:Calcimycin; D014700:Verapamil; D009543:Nifedipine; D007545:Isoproterenol; D002118:Calcium; D004837:Epinephrine