Antiadrenergic action of adenosine on ventricular myocardium in embryonic chick hearts

Abstract

Adenosine, a physiological metabolite, is known to exert a negative inotropic effect on atrial muscle [5, 7], to impair atrioventricular conduction [2, 7, 17] and depress pacemaker activity [18]. In addition to such direct actions, adenosine is also known to modulate several of the actions of catecholamines in different tissues [9, 15, 16]. In ventricular muscle, adenosine attenuates the inotropic effect of catecholamines, but has no contractile effect in the absence of catecholamines [1, 6, 15]. Thus, adenosine appears to exert its functions in heart by direct [2, 5, 7, 18] and indirect (anti-adrenergic) [1, 11, 15] mechanisms. The isoproterenol-induced increase in ventricular contractility is associated with an increase in cyclic AMP (cAMP) [19]. Since isoproterenol, cAMP analogs, and cAMP itself (applied internally), increase the Ca 2+-inward current (Isi) and slow action potentials, a causal relationship between cAMP and Isi has been proposed [10]. The ability of isoproterenol to restore excitability to partially depolarized cardiac fibers and/or enhance pre-existing slow action potentials is attributed to increase in cAMP that leads to an increase in the Isi. Adenosine decreased the cAMP levels of catecholamine-treated hearts [1, 6, 15] but unexpectedly adenosine had no inhibitory effect on slow action potentials obtained in elevated K + (27 mM) plus 10 −7 to 10 −6 M isoproterenol solution [12, 13]. In the present study, we wanted to find out whether adenosine would attenuate ventricular slow action potentials enhanced by relatively low concentrations of isoproterenol in normal K + solution. We set out to confirm in parallel experiments that adenosine also reduces the cAMP content of hearts exposed to isoproterenol.