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• W2034315036 abstract "Recent studies showed that chronic β-adrenoceptor (AR) blocker treatment exerts beneficial effects in patients with chronic heart failure (CHF). In CHF, sympathetic drive to the heart is increased, and this causes pathological changes in cardiac β-AR-G-protein(s)-adenylyl cyclase system: Cardiac β-1 AR are decreased, and amount and activity of cardiac Gi-protein and G-protein-coupled receptor kinase (GRK) are increased resulting in diminished cardiac β-AR functional responsiveness. One possible mechanism of beneficial effects of β-AR blockers could be that they prevent adverse effects of increased sympathetic activity and up-regulate cardiac (and vascular) β-AR density, and by this, enhance β-AR-mediated effects. Another possibility could be that chronic β-AR blocker treatment normalizes activity of Gi-protein and may thereby restore β-AR functional responsiveness. Moreover, failing human heart exhibits an inverse force–frequency relationship. β-AR blockers reduce heart rate; this may, therefore, improve force of contraction. One of the strongest stimuli to activate GRK is increased sympathetic activity (as in CHF) via β-AR stimulation. β-AR blockers, by blocking β-AR, can prevent GRK activation and/or can reduce the (previously enhanced) GRK activity, and this might—at least partly—contribute to beneficial effects of β-AR blockers in CHF treatment. Finally, the “loss-of-function” Arg389Gly β-1 AR polymorphism seems to determine heart rate and blood pressure responses to β-1 AR blocker administration: Arg389Arg β-1 AR subjects exhibit stronger effects than subjects with one or two Gly389 alleles. Thus, it might be predicted that patients homozygous Arg389 β-1 AR should be good responders, whereas patients homozygous Gly389 β-1 AR polymorphism should be poor or non-responders." @default.
• W2034315036 created "2016-06-24" @default.
• W2034315036 creator A5063355903 @default.
• W2034315036 date "2007-01-11" @default.
• W2034315036 modified "2023-10-16" @default.
• W2034315036 title "β-adrenoceptor blocker treatment and the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure" @default.
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• W2034315036 doi "https://doi.org/10.1007/s00210-006-0125-7" @default.
• W2034315036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17216434" @default.
• W2034315036 hasPublicationYear "2007" @default.
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