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

Nakamura S, Nakamura I, Ma L, Vaughan DE, Fogo AB
Kidney Int. 2000 58 (1): 251-9

PMID: 10886570 · DOI:10.1046/j.1523-1755.2000.00160.x

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 PAI-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 PAI-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. 01 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.

MeSH Terms (22)

Angiotensin II Animals Aorta Blood Pressure Blotting, Northern Extracellular Matrix Proteins Gene Expression Hypertension, Renal In Situ Hybridization Kidney Liver Male Myocardium Plasminogen Activator Inhibitor 1 Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin Renin-Angiotensin System RNA, Messenger Vasoconstrictor Agents

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