ANGIOTENSIN-II INDUCES FIBRONECTIN EXPRESSION ASSOCIATED WITH CARDIACFIBROSIS IN THE RAT

Fibronectin expression was studied in the heart of rats given a contin uous infusion of angiotensin II (Ang II). Northern blot analysis showe d that left ventricular fibronectin steady-state mRNA increased fivefo ld to eightfold in response to pressor doses of Ang II after 24 hours. Accumulation of immunodetectable fibronectin in the ventricles occurr ed after the mRNA levels increased. The changes in fibronectin express ion were reversible when Ang II treatment was withdrawn. The Ang II-in duced increase in fibronectin mRNA accompanied similar increases for c ollagen type I, collagen type IV, and atrial natriuretic factor steady -state mRNA. Interstitial and perivascular fibrosis was identified in both ventricles of angiotensin-treated rats within 3 days. In situ hyb ridization identified cells associated with areas of fibrosis as the p rincipal site of fibronectin mRNA accumulation in treated animals. By comparison, normal hearts showed fibronectin expression primarily with in ventricular vascular tissue and the atrial endocardium. A dose-depe ndent reduction of fibronectin expression followed treatment with losa rtan, indicating an Ang II type 1 receptor-mediated effect. Normalizat ion of blood pressure during Ang II infusion by either hydralazine or prazosin had different effects on the level of fibronectin steady-stat e mRNA, indicating that blood pressure elevation was not the principal factor responsible for fibronectin induction. Concurrent administrati on of angiotensin-converting enzyme inhibitors with Ang II attenuated the increased fibronectin expression. Our data indicate that Ang II in duces an acute fibrotic response within the heart and suggests that An g II stimulates fibronectin expression within nonmyocytic cardiac cell s by a direct action.