TY - JOUR
T1 - Angiotensin-ii induction of plasminogen activator inhibitor-1 gene expression in astroglial cells of normotensive and spontaneously hypertensive rat brain
AU - Zelezna, Blanka
AU - Rydzewski, Bartosz
AU - Lu, Di
AU - Olson, John A.
AU - Shiverick, Kathleen T.
AU - Tang, Wei
AU - Sumners, Colin
AU - Raizada, Mohan K.
PY - 1992/12/1
Y1 - 1992/12/1
N2 - Angiotensin-II (AII) 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 AII type 1 (AT1) receptors. Since abnormal expression of the brain AII system has been demonstrated in spontaneously hypertensive (SH) rats, we investigated the regulation of PAI-1 gene expression by AII in astroglial cells from the brains of these animals. AII 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 AII-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 AII-modulated PAI-1 levels in SH rat astroglia is consistent with a proposed role of these interactions in the development of hypertension in these animals.
AB - Angiotensin-II (AII) 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 AII type 1 (AT1) receptors. Since abnormal expression of the brain AII system has been demonstrated in spontaneously hypertensive (SH) rats, we investigated the regulation of PAI-1 gene expression by AII in astroglial cells from the brains of these animals. AII 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 AII-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 AII-modulated PAI-1 levels in SH rat astroglia is consistent with a proposed role of these interactions in the development of hypertension in these animals.
UR - http://www.scopus.com/inward/record.url?scp=0027076463&partnerID=8YFLogxK
U2 - 10.1210/mend.6.12.1491687
DO - 10.1210/mend.6.12.1491687
M3 - Article
C2 - 1491687
AN - SCOPUS:0027076463
SN - 0888-8809
VL - 6
SP - 2009
EP - 2017
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 12
ER -