LOCALIZATION OF THE ANGIOTENSIN-II RECEPTOR SUBTYPES IN THE HUMAN ATRIUM

Angiotensin II has two major receptor subtypes, designated AT(1) and A T(2). Both have been detected in the heart of several species, but mos t of the known functions of angiotensin II seem to be mediated through the AT(1) receptor. The major objective of this study was to specify the cell type on which the AT(2) receptor is located in the atrium of human heart. Right atrial biopsies from patients with coronary artery disease were tested in membrane binding assays and found to contain hi gh levels of angiotensin II receptor (820+/-175 fmol/mg), 82+/-2% of w hich was of the AT(2) subtype. Cryostat sections of these biopsies wer e incubated with I-125-[Sar(1),Ile(8)] angiotensin II in the presence of selective concentrations of the cold ligands losartan and CGP 42112 A to detect the subtypes using microscopic autoradiography. High local densities of the AT(2) receptor were observed. Comparison of the labe lling patterns thus obtained with adjacent sections stained for viment in, collagen, neurofilaments or acetylcholinesterase revealed that the high densities of AT(2) receptor were always associated with fibrous tissue. However, the AT(1) receptor was in general evenly distributed over the tissue at low concentrations. Higher local concentrations of this receptor subtype were observed on nervous tissue. The present fin ding of high densities of the AT(2) receptor on fibroblasts at sites o f fibrosis may have important clinical implications. Further studies t o elucidate the function of this receptor subtype in the heart are the refore essential and the clinical consequences of the use of AT(1) ant agonists on post-infarction remodelling should be investigated. (C) 19 96 Academic Press Limited