Changes in cardiac beta-adrenoceptors in human heart diseases: relationship to the degree of heart failure and further evidence for etiology-related regulation of beta 1 and beta 2 subtypes.
Radioligand binding studies were performed to investigate total beta-adrenoceptor density (Bmax) and beta 1 and beta 2 subtype distribution in left ventricular biopsies obtained from 8 prospective transplant donors serving as controls and from 143 patients with different degrees of heart failure (NYHA class II to IV) undergoing aortic or mitral valve surgery due to aortic or mitral stenosis, aortic or mitral regurgitation, as well as combined aortic or mitral valve lesions (stenosis and regurgitation). In 13 other patients, heart failure was due to hypertrophic obstructive cardiomyopathy (N = 6, NYHA III), tetralogy of Fallot (N = 4, NYHA III), or Becker's muscular dystrophy (N = 3, NYHA IV). Bmax was assessed by (-)-(125I)-iodocyanopindolol used as radioligand. Competition experiments with the highly selective beta 1-adrenoceptor antagonist CGP 20712A were performed for determination of beta 1- and beta 2-adrenoceptor subtypes. In biopsies taken from transplant donors, the Bmax was found to be 70.1 +/- 5.8 fmol/mg protein. In all groups investigated the extent of total beta-adrenoceptor downregulation was related to the degree of heart failure. The decrease in Bmax was found to be about 20% (NYHA II), 45% (NYHA III), and 60% (NYHA IV) when compared with controls. There was no significant difference in the reduction of total beta-adrenoceptor density between isolated aortic or mitral valve diseases and combined valve lesions. Independent of the degree of heart failure, selective downregulation of the beta 1 subtype was found in patients with isolated or combined aortic valve diseases, hypertrophic obstructive cardiomyopathy, and Becker's muscular dystrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Steinfath
M
M
Department of Anesthesiology, University of Hamburg, Germany.
Lavicky
J
J
Schmitz
W
W
Scholz
H
H
Döring
V
V
Kalmár
P
P
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001021:Aortic Valve; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications; D015536:Down-Regulation; D005260:Female; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism*; D006349:Heart Valve Diseases / Q000150:complications; D006352:Heart Ventricles; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020120:Iodocyanopindolol; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve; D009136:Muscular Dystrophies / Q000150:complications; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis* / Q000378:metabolism; D013771:Tetralogy of Fallot / Q000150:complications
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D020120:Iodocyanopindolol; D010869:Pindolol; C049763:CGP 20712A; C033394:CGP 12177