The increase in rat ventricular automaticity induced by salbutamol is mediated through β1- but not β2-adrenoceptors: Role of phosphodiesterases
| Autor: | Carmen Gonzalez-Muñoz, Santiago Medin-Aguerre, Jesús Hernández-Cascales, Teodomiro Fuente |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Agonist medicine.medical_specialty Phosphodiesterase Inhibitors medicine.drug_class Heart Ventricles Phosphodiesterase 3 In Vitro Techniques Pharmacology General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley chemistry.chemical_compound Theophylline Internal medicine Cyclic AMP medicine Animals Ventricular Function Albuterol General Pharmacology Toxicology and Pharmaceutics Adrenergic beta-2 Receptor Agonists Rolipram Cilostamide Dose-Response Relationship Drug Phosphoric Diester Hydrolases Chemistry Antagonist Phosphodiesterase General Medicine Adrenergic beta-1 Receptor Antagonists Rats Endocrinology Milrinone Female Receptors Adrenergic beta-2 Receptors Adrenergic beta-1 medicine.drug |
| Zdroj: | Life Sciences. 88:1095-1101 |
| ISSN: | 0024-3205 |
| Popis: | Aims 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. Main methods Experiments were performed in the spontaneously beating isolated right ventricle of the rat heart. We also measured cAMP production in this tissue. Key findings The β 2 -AR agonist salbutamol (1-100 μM) produced a concentration-dependent increase in ventricular automaticity that was not affected by 50 nM 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 CGP20712A. 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. Significance 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. |
| Databáze: | OpenAIRE |
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