Nitric oxide mediates the anti-adrenergic effect of adenosine on calcium current in isolated rabbit atrioventricular nodal cells

The aim of this study was to determine if adenosine exerts an anti-adrenergic effect on rabbit isolated atrioventricular (AV) nodal cells and, if so, the dependence of this effect on nitric oxide (NO) production. Inward Ca current,I _Ca, was measured in AV nodal cells, enzymatically isolated from rabbit hearts. Isoprenaline (0.1 M) increasedI _Ca from 676 ± 59 to 1102 ± 86 pA (n = 25). This isoprenaline-induced increase inI _Ca, (178 ± 15 % of control) was abolished in the presence of 10 M adenosine (I _Ca 100 ± 2 % of control,n = 9, P < 0.05). This effect of adenosine was completely blocked by the A₁ receptor antagonist CPDPX (8-cyclopentyl 1, 3-dipropylxanthine, 0.1 M). In cells pre-treated with the NO synthase inhibitor,l-nitro-arginine methyl ester (l-NAME, 1 mM) the isoprenaline-induced increase inI _Ca(208 ± 39 % of control,n = 7) was not reduced by the addition of 10 M adenosine (195 ± 32% of control). Co-incubation of cells inl-NAME withl--arginine (1 mM, the endogenous substrate of NO synthase) restored the adenosine-induced attenuation ofI _Ca. In these cells, isoprenaline increasedI _Ca (157 ± 7% of control,n = 6), and, following addition of adenosine (10 M)I _Ca was reduced to 107 ± 8% (P < 0.05). The NO-releasing agent SIN-1 (3-morpholino-sydnonimine, 100 M) inhibitedI _Ca augmented by isoprenaline (n = 5). It is concluded that adenosine exerts an anti-adrenergic effect on the AV node via A, receptors to attenuate a catecholamine-stimulated increase inI _Ca and that this action involves the intracellular production of NO.