Localization of the Angiotensin II Receptor Subtypes in the Human Atrium

Angiotensin II has two major receptor subtypes, designated AT1and AT2. Both have been detected in the heart of several species, but most of the known functions of angiotensin II seem to be mediated through the AT1receptor. The major objective of this study was to specify the cell type on which the AT2receptor 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 high levels of angiotensin II receptor (820±175 fmol/mg), 82±2% of which was of the AT2subtype. Cryostat sections of these biopsies were incubated with125I-[Sar1,Ile8] angiotensin II in the presence of selective concentrations of the cold ligands losartan and CGP 42112A to detect the subtypes using microscopic autoradiography. High local densities of the AT2receptor were observed. Comparison of the labelling patterns thus obtained with adjacent sections stained for vimentin, collagen, neurofilaments or acetylcholinesterase revealed that the high densities of AT2receptor were always associated with fibrous tissue. However, the AT1receptor 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 finding of high densities of the AT2receptor on fibroblasts at sites of fibrosis may have important clinical implications. Further studies to elucidate the function of this receptor subtype in the heart are therefore essential and the clinical consequences of the use of AT1antagonists on post-infarction remodelling should be investigated.