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 mu M) increased I-Ca from 676 +/- 59 to 1102 +/- 86 pA (n = 25). This isoprenaline-induced increase in I-Ca(178 +/- 15% of control) was abolished in the presence of 10 mu M adenosine (I-Ca 100 +/- 2% of control, n = 9, P < 0.05). This effect of adenosine was completely blocked by the A(1) receptor antagonist CPDPX (8-cyclopentyl 1, 3-dipropylxanthine, 0.1 mu M) In cells pre-treated with the NO synthase inhibitor, L-nitro-arginine methyl ester (L-NAME, 1 mM) the isoprenaline-induced increase in I-Ca(208 +/- 39% of control, n = 7) was not reduced by the addition of 10 mu M adenosine (195 +/- 32% of control). Co-incubation of cells in L-NAME with L-arginine (1 mM, the endogenous substrate of NO synthase) restored the adenosine-induced attenuation of l(Ca). In these cells, isoprenaline increased I-Ca (157 +/- 7% of control, n = 6), and, following addition of adenosine (10 mu M) I-Ca was reduced to 107 +/- 8% (P<0.05). The NO-releasing agent SIN-1 (3-morpholino-sydnonimine, 100 mu M), inhibited I-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 in I-Ca and that this action involves the intracellular production of NO.
