ANGIOTENSIN-II ALTERS AORTIC FIBRONECTIN INDEPENDENTLY OF HYPERTENSION

We performed these studies to assess the potential role of hemodynamic forces in mediating the changes in aortic fibronectin mRNA expression that occur in the rat in response to angiotensin II administration. With the use of an acute hypertensive model involving a 3-day infusion with a presser dose of angiotensin II given by osmotic minipump, a selective increase in fibronectin mRNA expression but not of several other extracellular matrix genes was documented. This change was inhibited by losartan, indicating the importance of angiotensin receptors in the response. Prazosin, hydralazine, or L-arginine added to the drinking water all lowered the angiotensin II-induced increase in blood pressure but did not attenuate the increase in fibronectin mRNA expression. Angiotensin-converting enzyme inhibition using trandolapril did reduce fibronectin mRNA in the angiotensin II-infusion model, despite an inability to reduce blood pressure, whereas when angiotensin I was infused, quinapril lowered both blood pressure and fibronectin expression even at doses that did not completely normalize blood pressure. These studies suggest that angiotensin II induced an increase in aortic fibronectin mRNA that was not dependent solely on blood pressure.