Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo

Background. The fibrinolytic system plays an important role in degrading fi brin-rich thrombi and in vascular and tissue remodeling. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regula te PAI-1 expression via the Ang type 1 (AT1) receptor in some tissues and v ia the AT4 receptor in cultured endothelium. The purpose of this study was to examine the tissue-specific pattern of PAI-1 expression in response to i nfusion of Ang II in vivo. Methods. Adult male Sprague-Dawley rats (N = 5 in each group) were treated with four hours of intravenous infusions of Ang II or vehicle control while mean arterial pressure (MAP) was monitored: group 1, 600 ng/kg/min Ang II; group 2, Ang II + 10 mg/kg of the ATI receptor antagonist (AT1RA) L158-809 q2 hour; group 3, Ang II + 0.01 to 0.1 mg/kg hydralazine as required to ma intain normal blood pressure; and group 4, saline-infused controls. After i nfusion, tissue was harvested for Northern blotting, immunohistochemical an alysis, and in situ hybridization. Results. In group 1, Ang II infusion increased MAP from 105 +/- 8 to 160 +/ - 9 mm Hg (mean +/- SE, P < 0.01). Ang II induced increased expression of P AI-1 mRNA in all tissues examined from 5.1-fold in the heart, 9.7-fold in t he kidney, 10.0-fold in the aorta, and up to 30.0-fold in the liver tall P < 0.01 vs. control). While both AT1RA (group 3) and hydralazine (group 3) p revented Ang II-induced elevation in blood pressure, the Ang II-dependent e xpression of PAI-1 mRNA was reduced by only AT1 receptor blockade. Conclusions. We conclude that in the rat, PAI-1 is induced in a variety of tissues by Ang II directly through the AT1 receptor, independent of its eff ects on blood pressure.