Academic Journal
Transregulation of adenylyl-cyclase-coupled inhibitory receptors in heart failure enhances anti-adrenergic effects on adult rat cardiomyocytes
| العنوان: | Transregulation of adenylyl-cyclase-coupled inhibitory receptors in heart failure enhances anti-adrenergic effects on adult rat cardiomyocytes |
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| المؤلفون: | Borst, Mathias M, Szalai, Palma, Herzog, Nicole, Kübler, Wolfgang, Strasser, Ruth H |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 1999 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Original Article |
| الوصف: | Objective: In congestive heart failure (CHF), a desensitisation of stimulatory β-receptors and of adenylyl cyclase in the heart is associated with an increase in inhibitory G i proteins. To investigate whether the regulation of the G i -mediated inhibitory side of the adenylyl cyclase system may be of functional importance in the failing myocardium, the contractile response of isolated adult cardiomyocytes to stimulation of inhibitory muscarinic M 2 and A 1 adenosine receptors was analysed. Methods: CHF was induced in rats by banding of the ascending aorta and was verified by doubling of lung wet weight. After four weeks, contraction amplitude (Δ L ) and the velocity (d L /d t max ) of isolated ventricular cardiomyocytes during electrical field stimulation in the presence of 1 mM Ca2+ were measured using video micrometry. Results: Contractile responses of failing cardiomyocytes to 5 mM Ca2+ were unchanged. The response to increasing concentrations of the β-adrenergic agonist, isoproterenol (0.1–30 nM), and to forskolin (0.1 nM–1 μM) were significantly blunted. When A 1 receptors were activated with N 6-( R -phenyl-isopropyl)-adenosine (PIA; 0.01–1 μM) in the presence of 3 nM isoproterenol, contractility was unchanged in cells compared with those from sham-operated rats, but Δ L was reduced by up to 23% and d L /d t max by 35% in failing cardiomyocytes ( P <0.01), demonstrating an enhanced inhibitory effect of A 1 receptors. The response to the M 2 receptor agonist, carbachol (0.01–3 μM), was augmented to a comparable extent (Δ L , −22%, d L /d t max , −39%; P <0.01). Conclusions: In CHF, the inotropic responses to β-receptor-stimulation and to direct stimulation of adenylyl cyclase, but not to Ca2+, are diminished due to desensitisation of the stimulatory side of the adenylyl cyclase signal transduction system. In parallel, the responses to inhibitory receptors are augmented, leading to a pronounced G i -mediated negative inotropic effect on failing heart muscle cells. Those anti-adrenergic effects could ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://cardiovascres.oxfordjournals.org/cgi/content/short/44/1/113; http://dx.doi.org/10.1016/S0008-6363(99)00197-2 |
| DOI: | 10.1016/S0008-6363(99)00197-2 |
| الاتاحة: | http://cardiovascres.oxfordjournals.org/cgi/content/short/44/1/113 https://doi.org/10.1016/S0008-6363(99)00197-2 |
| Rights: | Copyright (C) 1999, European Society of Cardiology |
| رقم الانضمام: | edsbas.454FB2BE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/S0008-6363(99)00197-2 |
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