Angiotensin-II induction of plasminogen activator inhibitor-1 gene expression in astroglial cells of normotensive and spontaneously hypertensive rat brain

Abstract

Angiotensin-II (All) stimulates plasminogen activator inhibitor-1 (PAI-1) gene transcription, translation, and protein secretion from astroglial cells derived from normotensive [Wistar-Kyoto (WKY)] rat brain, an effect mediated by All type 1 (AT1) receptors. Since abnormal expression of the brain All system has been demonstrated in spontaneously hypertensive (SH) rats, we investigated the regulation of PAI-1 gene expression by All in astroglial cells from the brains of these animals. All caused an increase in PAI-1 gene expression in SH rat astroglia in a manner similar to that observed in WKY-derived cultures. However, both the basal and All-stimulated levels of PAI-1 mRNA in SH rat astroglia were only 20% of those observed in WKY rat astroglial cultures. Consequently, there was a significant reduction in the de novo synthesis and secretion of PAI-1 from astroglia of SH rat brain. The reduced synthesis and secretion of PAI-1 from SH rat brain astroglia was associated with lower numbers of AT1 receptors in these cells. However, the steady state levels of AT1 receptor mRNA were comparable in both WKY and SH rat astroglia. This reduction in All-modulated PAI-1 levels in SH rat astroglia is consistent with a proposed role of these interactions in the develop-ment of hypertension in these animals. Copyright © 1992 by The Endocrine Society.