Development of beta-adrenoceptor number and subtype distribution in the transplanted human heart.
The transplanted human heart is a denervated organ and thus may exhibit beta-adrenoceptor supersensitivity. To monitor possible beta-adrenoceptor changes in the transplanted human heart we assessed, in right ventricular endomyocardial biopsies from eight heart transplant recipients, beta-adrenoceptor number (by (-)-[125I]-iodocyanopindolol [ICYP] binding) and beta 1:beta 2-adrenoceptor ratio (by inhibition of ICYP binding with a beta 1-adrenoceptor saturating concentration of CGP 20712 A, 500 nM) in weekly, later monthly, intervals for 6-18 post-transplant months. In the biopsies of the transplanted hearts, beta-adrenoceptor number was significantly higher than in the right ventricular membranes of the explanted native hearts of the patients; during the whole period, the biopsies' beta-adrenoceptor number was quite stable and no significant increase or decrease was observed. In contrast, with increasing post-transplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20%, while after 4-18 months it had decreased to 66:34%. We conclude that in the first 18 post-transplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decrease in beta 1- and increase in beta 2-adrenoceptors with increasing post-transplant time. This may have important pathophysiological consequences for regulation of contractility and/or heart rate by endogenous catecholamines in heart transplant recipients.
Zerkowski
H R
HR
Abtlg. Nieren- und Hochdruckkrankheiten, Universitätsklinikum Essen, Germany.
Khamssi
M
M
Brodde
O E
OE
D000293:Adolescent; D000328:Adult; D016027:Heart Transplantation / Q000473:pathology; D006352:Heart Ventricles / Q000737:chemistry / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta