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, ICa, was measured in AV nodal cells, enzymatically isolated from rabbit hearts. Isoprenaline (0.1 microM) increased ICa from 676 +/-59 to 1102 +/-86 pA (n =25). This isoprenaline-induced increase in ICa(178 +/-15% of control) was abolished in the presence of 10 microM adenosine (ICa100 +/-2% of control, n =9, P <0.05). This effect of adenosine was completely blocked by the A1 receptor antagonist CPDPX (8-cyclopentyl l, 3-dipropylxanthine, 0.1 microM). In cells pre-treated with the NO synthase inhibitor, L-nitro-arginine methyl ester (L-NAME, 1 mM) the isoprenaline-induced increase in ICa(208 +/-39% of control, n=7) was not reduced by the addition of 10 microM 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 ICa. In these cells, isoprenaline increased ICa (157 +/-7% of control, n =6), and, following addition of adenosine (10 microM) ICa was reduced to 107 +/-8% (P <0.05). The NO-releasing agent SIN-1 (3-morpholino-sydnonimine, 100 microM), inhibited ICa augmented by isoprenaline (n=5). It is concluded that adenosine exerts an anti-adrenergic effect on the AV node via A1 receptors to attenuate a catecholamine-stimulated increase in ICa and that this action involves the intracellular production of NO.
Martynyuk
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AE
Department of Medical Cardiology, Royal Infirmary, Glasgow, UK.
Kane
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KA
Cobbe
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SM
Rankin
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AC
D000241:Adenosine / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001283:Atrioventricular Node / Q000166:cytology*; D015220:Calcium Channels / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D014970:Xanthines / Q000494:pharmacology
D018674:Adrenergic Antagonists; D015220:Calcium Channels; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester