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  • 1
    ISSN: 1432-1041
    Keywords: Key words Metoprolol ; Cardiomyopathy ; G-proteins; β-adrenoceptor density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In human heart failure downregulation of β-adrenoceptors and upregulation of Gi-protein α-subunits (Giα) results desensitization of the myocardial β-adrenergic signal transduction pathway and reduced positive inotropic effects of catecholamines. Metoprolol treatment has been shown to restore the reduced β-adrenoceptor density in dilated cardiomyopathy. The main objective of the present study was to investigate whether metoprolol also decreases the elevated inhibitory Giα levels in patients suffering from congestive heart failure. Methods: Total Giα was determined by pertussis toxin-catalysed ADP ribosylation and β1- and β2-adrenoceptor densities by radioligand binding in right ventricular myocardial biopsies of 18 patients with dilated or ischaemic cardiomyopathy (NYHA II–IV) before and after 3 months of therapy. Nine controls were treated with conventional therapy only [diuretics, digitalis, nitrates, angiotensin-converting enzyme (ACE) inhibitors], and nine received the β1-selective blocker metoprolol in addition (mean 98 ± 12 mg daily). Results: In biopsies from patients treated with metoprolol, Giα significantly decreased to 74% of predrug value and total β-adrenoceptor increased by a selective increase in β1- adrenoceptors (44.7 vs 34.0 fmol ⋅ mg−1 protein). These effects were accompanied by significantly increased oxygen uptake at the anaerobic threshold (8.65 vs 6.95 ml ⋅ kg−1⋅ min−1). In the control group no significant changes in biochemical and clinical parameters occurred. Conclusion: Metoprolol partly reverses Giα-upregulation and β-adrenoceptor downregulation in heart failure, which might contribute to the clinical improvement of patients treated with β-blockers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Captopril ; Dilated cardiomyopathy ; ACE-inhibitors ; G-proteins ; β-adrenoceptor density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In end-stage heart failure due to idiopathic dilated cardiomyopathy β1-adrenoceptors are downregulated and G1α-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on β-adrenoceptor density and Giα-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II–III) were studied before and after 8–11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5–50 mg per day, (divided in 2–3 doses) p.o. in addition to “conventional” therapy with digoxin and diuretics, and 10 controls received “conventional” therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total β-adrenoceptor density by selectively increasing β1-adrenoceptors (31.6 vs 41.2 fmol·mg−1; p〈0.05) but had no significant effect on Giα-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial β1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.
    Type of Medium: Electronic Resource
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