Cyclic AMP levels in ventricular myocytes from noradrenaline-treated guinea-pigs
| Autor: | F. Del Monte, Sian E. Harding, Dylan G. Wynne |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Inotrope
Male medicine.medical_specialty Sympathetic nervous system IBMX Phosphodiesterase Inhibitors Heart Ventricles Guinea Pigs Biology Contractility chemistry.chemical_compound Norepinephrine Internal medicine Isoprenaline medicine Cyclic AMP Myocyte Animals Phosphodiesterase inhibitor Pharmacology Isoproterenol medicine.anatomical_structure Endocrinology chemistry Catecholamine medicine.drug |
| Zdroj: | European journal of pharmacology. 310(2-3) |
| ISSN: | 0014-2999 |
| Popis: | Chronic activation of the sympathetic nervous system in human heart failure is believed to cause cardiac beta-adrenoceptor desensitisation. We have investigated the relationship between beta-adrenoceptor desensitisation and cyclic AMP levels in cardiac myocytes isolated from the ventricle of guinea-pigs chronically infused with noradrenaline hydrochloride for 7 days. Functional beta-adrenoceptor desensitisation was confirmed by a significant decrease in the maximum isoprenaline-stimulated contraction amplitude and an increased EC50 for isoprenaline. In the absence of beta-adrenoceptor stimulation, basal cyclic AMP levels were significantly depressed in populations of myocytes from noradrenaline-treated animals compared to sham-operated controls, and this was not accounted for by myocyte hypertrophy or necrosis. Similarly, there was a significant decrease in cyclic AMP levels at maximally inotropic isoprenaline concentrations. Threshold and maximum inotropic concentrations of the phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine (IBMX), restored isoprenaline-stimulated cyclic AMP levels in noradrenaline-treated guinea-pig cardiac myocytes, although we have previously reported no increase in maximum inotropic effect of isoprenaline with these compounds. |
| Databáze: | OpenAIRE |
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