| Title |
Carvedilol induces greater control of β2- than β1-adrenoceptor-mediated inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human failing myocardium
|
|---|---|
| Published in |
Naunyn-Schmiedeberg's Archives of Pharmacology, March 2014
|
| DOI | 10.1007/s00210-014-0974-4 |
| Pubmed ID | |
| Authors |
Peter Molenaar, Torsten Christ, Emanuel Berk, Andreas Engel, Katherine T. Gillette, Alejandro Galindo-Tovar, Ursula Ravens, Alberto J. Kaumann |
| Abstract |
The β-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 μM) or PDE4-selective inhibitor rolipram (1 μM) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1-adrenoceptors (β2-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2-adrenoceptors (β1-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from -logEC50s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-β-blocker-treated patients, consistent with the previously reported β2-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular β2-adrenoceptors compared to β1-adrenoceptors. The β2-adrenoceptor-selectivity of carvedilol may provide protection against β2-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Denmark | 1 | 4% |
| Unknown | 23 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 25% |
| Student > Ph. D. Student | 3 | 13% |
| Student > Doctoral Student | 3 | 13% |
| Professor | 2 | 8% |
| Professor > Associate Professor | 2 | 8% |
| Other | 5 | 21% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 25% |
| Biochemistry, Genetics and Molecular Biology | 4 | 17% |
| Agricultural and Biological Sciences | 3 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 8% |
| Nursing and Health Professions | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 6 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 March 2014.
All research outputs
#15,298,293
of 22,751,628 outputs
Outputs from Naunyn-Schmiedeberg's Archives of Pharmacology
#1,340
of 1,723 outputs
Outputs of similar age
#132,025
of 224,565 outputs
Outputs of similar age from Naunyn-Schmiedeberg's Archives of Pharmacology
#11
of 11 outputs
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