In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 17 ( 1998-10-27), p. 1735-1741
Abstract:
Background —The regulation and interaction of ACE and the angiotensin II (Ang II) type I (AT 1 ) receptor in the failing human heart are not understood. Methods and Results —Radioligand binding with 3 H-ramiprilat was used to measure ACE protein in membrane preparations of hearts obtained from 36 subjects with idiopathic dilated cardiomyopathy (IDC), 8 subjects with primary pulmonary hypertension (PPH), and 32 organ donors with normal cardiac function (NF hearts). 125 I-Ang II formation was measured in a subset of hearts. Saralasin ( 125 I-{Sar 1 ,Ile 8 }-Ang II) was used to measure total Ang II receptor density. AT 1 and AT 2 receptor binding were determined with the AT 1 receptor antagonist losartan. Maximal ACE binding ( B max ) was 578±47 fmol/mg in IDC left ventricle (LV), 713±97 fmol/mg in PPH LV, and 325±27 fmol/mg in NF LV ( P 〈 0.001, IDC or PPH versus NF). In IDC, PPH, and NF right ventricles (RV), ACE B max was 737±78, 638±137, and 422±49 fmol/mg, respectively ( P =0.02, IDC versus NF; P =0.08, PPH versus NF). 125 I-Ang II formation correlated with ACE binding sites ( r =0.60, P =0.00005). There was selective downregulation of the AT 1 receptor subtype in failing PPH ventricles: 6.41±1.23 fmol/mg in PPH LV, 2.37±0.50 fmol/mg in PPH RV, 5.38±0.53 fmol/mg in NF LV, and 7.30±1.10 fmol/mg in NF RV ( P =0.01, PPH RV versus PPH LV; P =0.0006, PPH RV versus NF RV). Conclusions —ACE binding sites are increased in both failing IDC and nonfailing PPH ventricles. In PPH hearts, the AT 1 receptor is downregulated only in the failing RV.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.98.17.1735
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1998
detail.hit.zdb_id:
1466401-X
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