Evidence for a cooperation between adenosine A₂ receptors and β₁‐adrenoceptors on cardiac automaticity in the isolated right ventricle of the rat

Abstract

maticity induced by a local injury in the isolated right ventricle of the rat were studied. 2 In concentrations ranging from 0.1 to 100 nM, NECA significantly increased ventricular automaticity. This effect was more reproducible when the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) was present at 5 nM, a concentration that blocks Al adenosine receptors.3 The excitatory effect of NECA was not observed when DPCPX was present at a concentration of 1O pM, which antagonizes both A1 and A2 adenosine receptors, as well as when rats were reserpinized. 4 In reserpinized rats, NECA increased ventricular automaticity in the presence of isoprenaline and the fl2-adrenoceptor antagonist, ICI-118,551, but not in the presence of the PI-adrenoceptor antagonists, bisoprolol or atenolol. 5 The A2a-selective adenosine receptor agonist, CGS-21680 (0.1 nM-10 Mm) was devoid of excitatory effect on ventricular automaticity. Binding studies of this compound to the rat ventricular membranes revealed that in the preparation there was no specific binding. 6 These results suggest that the excitatory effect of NECA on ectopic ventricular automaticity is dependent on endogenous catecholamines and is mediated by an A2 adenosine receptor which is in some way 'linked' to the P3-adrenoceptor. These A2 receptors do not appear to be of the A2a adenosine receptor subtype.

Haemodynamic effects of a selective adenosine A2A receptor agonist, CGS 21680, in chronic heart failure in anaesthetized rats

“…Certainly, an increase in heart rate can be due to a direct effect on the heart, or a reflex‐mediated activation of the sympathetic nervous system as a result of arterial dilatation and the lowering of blood pressure. Evidence from our laboratory (Nekooeian & Tabrizchi, 1996; Tabrizchi, 1997) and the laboratories of other investigators (Hutchison et al , 1989; Webb et al , 1991; Fozard & Carruthers, 1993; Hernandez et al , 1994) support the view that CGS 21680‐induced tachycardia is the result of reflex‐mediated activation of the sympathetic nervous system rather than a direct effect on the myocardium. However, we believe that the increase in heart rate by CGS 21680 was not the sole mechanism responsible for the increase in cardiac output during the administration of CGS 21680 in animals with chronic heart failure.…”

The increase in rat ventricular automaticity induced by salbutamol is mediated through β1- but not β2-adrenoceptors: Role of phosphodiesterases

“…His-Purkinje fibers contained in this tissue are able to beat spontaneously, and β-AR agonists increase their frequency by enhancing cAMP production (for review see DiFrancesco, 2010). In fact, cAMP itself as well as the β-AR agonists, isoproterenol or noradrenaline, increase the spontaneous frequency in this preparation (Hernández et al, 1989;Hernandez et al, 1994). It is known that the increase in cAMP levels, resulting from activation of β-AR, inhibit the inwardly rectifying potassium current (IK i ) which is responsible for generating the resting membrane potential (Koumi et al, 1995) and also enhances the cyclic nucleotide dependent current (I f ) (Hoppe et al, 1998).…”

“…Abnormal automaticity is an important mechanism underlying cardiac arrhythmias, and cAMP increases the spontaneous firing rate of pacemaker cells (DiFrancesco, 2010). The right ventricle of the rat contains pacemaker cells in the His-Purkinje fibers, which develop spontaneous activity resembling an idioventricular rhythm (Mangoni and Nargeot, 2008) and is a useful experimental model for assessing the pro-arrhythmic effect of cAMP producing agents (Hernandez et al, 1994;Hernandez and Ribeiro, 1996). The aims of the present study were to evaluate the effects of β 1 -and β 2 -AR activation on ventricular automaticity in this tissue and to examine whether these effects were modified by theophylline or PDE3-4 inhibition.…”

Resveratrol enhances the inotropic effect but inhibits the proarrhythmic effect of sympathomimetic agents in rat myocardium

“…For this, its atrial end was fixed to a metallic support and the apical end was attached to a Grass FT 03 force–displacement transducer. No electrical stimulation was applied (Hernàndez et al, 1994; Gonzalez-Muñoz et al, 2011). The right atria was isolated and suspended in an organ bath.…”

“…Abnormal automaticity is an important mechanism underlying cardiac arrhythmias and cAMP increases the spontaneous firing rate of pacemaker cells (DiFrancesco, 2010). The right ventricle of the rat contains pacemaker cells in the His-Purkinje fibres, which develop spontaneous activity resembling an idioventricular rhythm (Mangoni & Nargeot, 2008), making it a useful experimental model for assessing the proarrhythmic or antiarrhythmic effects of different agents (Hernàndez et al, 1994; Gonzalez-Muñoz et al, 2011). The aims of the present work were to investigate the effects of resveratrol on the inotropic and proarrhythmic effects of the sympathetic neurotransmitter noradrenaline (exogenously applied or endogenously released by tyramine), and on the effect of the β -adrenoceptor agonist, isoproterenol.…”