IDENTIFICATION OF FUNCTIONAL ANGIOTENSIN-II RECEPTORS ON RAT CARDIAC FIBROBLASTS

Background. Cardiac hypertrophy results in an increased deposition of the extracellular matrix (ECM) proteins fibronectin and collagen. Recent evidence indicates that angiotensin II (Ang II) might have an important role in the development of myocardial fibrosis accompanying cardiac hypertrophy. We sought to determine whether fibroblasts of cardiac origin (isolated from neonatal and adult animals) express receptors for Ang II and to examine the ability of this peptide to regulate fibronectin and collagen gene expression in a cultured adult cardiac fibroblast cell preparation. Methods and Results. Binding of I-125-Ang II to both neonatal and adult cardiac fibroblasts in culture was specific, reversible, and saturable, with the receptor evenly distributed over the cell population. Competition binding experiments with receptor-specific antagonists indicate that Ang II receptors found on both fibroblast types were of the AT(1) subtype. Analysis of mRNA levels for the AT(1) receptor indicates that adult cardiac fibroblasts express higher levels of the message than neonatal fibroblasts or cardiac myocytes. Addition of 10(-9) mol/L Ang II to adult cardiac fibroblasts resulted in an induction of ECM proteins above control levels, as determined through Northern blots and total collagen assays. Conclusions. Results from this study indicate that neonatal and adult rat cardiac fibroblasts in culture express ATI receptors for Ang II. Ang II stimulation of AT(1) receptors results in an increased gene expression for ECM proteins. These data suggest that Ang II might have important regulatory roles over cardiac fibroblast function under normal and pathological conditions.