Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins in patients with mild to moderate heart failure due to dilated cardiomyopathy.
In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1-adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-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 beta-adrenoceptor density by selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05) but had no significant effect on Gi alpha-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial beta 1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.
Jakob
H
H
Department of Pharmacology, Universitäts-Krankenhaus Eppendorf, University of Hamburg, Germany.
Sigmund
M
M
Eschenhagen
T
T
Mende
U
U
Patten
M
M
Schmitz
W
W
Scholz
H
H
Schulte am Esch
J
J
Steinfath
M
M
Hanrath
P
P
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D002216:Captopril / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D002216:Captopril; D019204:GTP-Binding Proteins