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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Galindo-tovar, A. Kaumann, A. J. |
| Description | Author Affiliation: Galindo-Tovar A ( Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.) |
| Abstract | BACKGROUND AND PURPOSE: beta(1) and beta(2)-adrenoceptors coexist in murine heart but beta(2)-adrenoceptor-mediated effects have not been detected in atrial and ventricular tissues, possibly due to marked phosphodiesterase (PDE) activity. We investigated the influence of the PDE3 inhibitor cilostamide and PDE4 inhibitor rolipram on the effects of (-)-adrenaline in three regions of murine heart. EXPERIMENTAL APPROACH: (-)-Adrenaline-evoked cardiostimulation was compared on sinoatrial beating rate, left atrial and right ventricular contractile force in isolated tissues from 129SvxC57B1/6 cross mice. Ventricular arrhythmic contractions were also assessed. KEY RESULTS: Both rolipram (1 microM) and cilostamide (300 nM) caused transient sinoatrial tachycardia but neither enhanced the chronotropic potency of (-)-adrenaline. Rolipram potentiated 19-fold (left atrium) and 7-fold (right ventricle) the inotropic effects of (-)-adrenaline. (-)-Adrenaline elicited concentration-dependent ventricular arrhythmias that were potentiated by rolipram. All effects of (-)-adrenaline were antagonized by the beta(1)-adrenoceptor-selective antagonist CGP20712A (300 nM). Cilostamide (300 nM) did not increase the chronotropic and inotropic potencies of (-)-adrenaline, but administered jointly with rolipram in the presence of CGP20712A, uncovered left atrial inotropic effects of (-)-adrenaline that were prevented by the beta(2)-adrenoceptor-selective antagonist ICI118551. CONCLUSIONS AND IMPLICATIONS: PDE4 blunts the beta(1)-adrenoceptor-mediated effects of (-)-adrenaline in left atrium and right ventricle but not in sinoatrial node. Both PDE3 and PDE4 reduce basal sinoatrial rate in a compartment distinct from the beta(1)-adrenoceptor compartment. PDE3 and PDE4, acting in concert, prevent left atrial beta(2)-adrenoceptor-mediated inotropy. PDE4 partially protects the right ventricle against (-)-adrenaline-evoked arrhythmias. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 153 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2008-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adrenergic Beta-1 Receptor Agonists Cardiotonic Agents Toxicity Epinephrine Myocytes, Cardiac Drug Effects Phosphodiesterase 4 Inhibitors Phosphodiesterase Inhibitors Pharmacology Tachycardia, Sinus Prevention & Control Tachycardia, Ventricular Adrenergic Beta-Agonists Adrenergic Beta-Antagonists Animals Cyclic Nucleotide Phosphodiesterases, Type 3 Metabolism Cyclic Nucleotide Phosphodiesterases, Type 4 Dose-Response Relationship, Drug Drug Synergism Heart Atria Heart Rate Heart Ventricles Imidazoles Isoproterenol Mice Mice, Inbred C57BL Myocardial Contraction Enzymology Phosphodiesterase 3 Inhibitors Adverse Effects Propanolamines Quinolones Receptors, Adrenergic, Beta-1 Receptors, Adrenergic, Beta-2 Rolipram Sinoatrial Node Chemically Induced Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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