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

Shinya Nakamura, Ikuko Nakamura, Lijun Ma, Douglas E. Vaughan, Agnes B. Fogo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Background: The fibrinolytic system plays an important role in degrading fibrin-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 regulate PAl-1 expression via the Ang type 1 (AT1) receptor in some tissues and via the AT4 receptor in cultured endothelium. The purpose of this study was to examine the tissue-specific pattern of PA1-1 expression in response to infusion 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 AT1 receptor antagonist (AT1RA) L158-809 q2 hour; group 3, Ang II + 0.01 to 0.1 mg/kg hydralazine as required to maintain normal blood pressure; and group 4, saline-infused controls. After infusion, tissue was harvested for Northern blotting, immunohistochemical analysis, 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 PAI-1 mRNA in all tissues examined from 5.1-fold in the heart, 9.7-fold in the kidney, 10.0-fold in the aorta, and up to 30.0-fold in the liver (all P < 0.0l vs. control). While both AT1RA (group 3) and hydralazine (group 4) prevented Ang II-induced elevation in blood pressure, the Ang II-dependent expression 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 effects on blood pressure.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalKidney international
Volume58
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Blood pressure
  • Extracellular matrix
  • Plasmin/plasminogen activator system
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Nephrology

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