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While β(2)-adrenoceptor (AR) agonists are useful bronchodilators, they also produce cardiac arrhythmias. These agents are not fully selective and also activate β(1)-AR, but the involvement of β(1)-AR and β(2)-AR in the observed pro-arrhythmic effect has not been established. We studied the effect of β(1)-AR and β(2)-AR activation on ventricular automaticity and the role of phosphodiesterases (PDE) in regulating this effect. Experiments were performed in the spontaneously beating isolated right ventricle of the rat heart. We also measured cAMP production in this tissue. The β(2)-AR agonist salbutamol (1-100 μM) produced a concentration-dependent increase in ventricular automaticity that was not affected by 50nM of the β(2)-AR antagonist ICI 118551. This effect was enhanced by the non-selective PDE inhibitor theophylline (100 μM) and by the selective PDE4 inhibitors rolipram (1 μM) and Ro 201724 (2 μM), but not modified by the selective PDE3 inhibitors cilostamide (0.3 μM) or milrinone (0.2 μM). The effects of salbutamol alone and in the presence of either theophylline or rolipram were virtually abolished by 0.1 μM β(1)-AR antagonist CGP 20712A. Salbutamol (10 μM) increased the cAMP concentration, and this effect was abolished by CGP 20712A (0.1 μM) but enhanced by theophylline (100 μM) or rolipram (1 μM). Cilostamide (0.3 μM) failed to modify the effect of salbutamol on cAMP concentration. These results indicate that the increase of ventricular automaticity elicited by salbutamol was exclusively mediated through β(1)-AR and enhanced by non-selective PDE inhibition with theophylline or selective PDE4 inhibition. However, PDE3 did not appear to regulate this effect. Copyright © 2011 Elsevier Inc. All rights reserved.


Carmen Gonzalez-Muñoz, Teodomiro Fuente, Santiago Medin-Aguerre, Jesús Hernández-Cascales. The increase in rat ventricular automaticity induced by salbutamol is mediated through β(1)- but not β(2)-adrenoceptors: role of phosphodiesterases. Life sciences. 2011 Jun 20;88(25-26):1095-101

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PMID: 21565204

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