TY - JOUR
T1 - Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency
AU - Brown, N. J.
AU - Bradford, J.
AU - Wang, Z.
AU - Lea, W.
AU - Ma, L.
AU - Ma, J.
AU - Vaughan, D. E.
AU - Fogo, A. B.
N1 - Funding Information:
This work was supported in part by NIH HL067308, HL060906, HL065193, DK044757, and DK056942.
PY - 2007/7
Y1 - 2007/7
N2 - Angiotensin (Ang) II stimulates plasminogen activator inhibitor-1 (PAI-1) expression in many cell types by mechanisms that are cell-type specific. We measured effects of Ang II or norepinephrine on PAI-1 expression in wild type (WT) and Ang type-1a receptor knockout mice (AT1a-/-) in the presence or absence of the non-specific AT1 antagonist losartan. Ang II and norepinephrine increased systolic blood pressure equally, whereas losartan decreased the pressor response of the former but not the latter in WT mice. In AT1a-/- mice, baseline systolic blood pressure was lower with no effect of Ang II, norepinephrine, or losartan. Ang II stimulated PAI-1 expression in the heart, aorta, and kidney and markedly in the liver of WT mice. In AT1a-/- mice, Ang II-stimulated PAI-1 was significantly attenuated compared with the WT in the heart and aorta but significantly enhanced in the kidney. Losartan decreased the induction in the aorta and liver of WT, and in the kidney and liver of AT1a-/- mice. Norepinephrine increased PAI-1 expression in WT heart and aorta, and in AT1a-/- heart, kidney, and liver with no effect of losartan. Renal PAI-1 expression correlated with AT1b receptor mRNA. We conclude that Ang II stimulates PAI-1 expression in part through the AT1b receptor in the kidney and liver. Further, norepinephrine induces PAI-1 expression in vivo with AT1a receptor deficiency modulating the effect.
AB - Angiotensin (Ang) II stimulates plasminogen activator inhibitor-1 (PAI-1) expression in many cell types by mechanisms that are cell-type specific. We measured effects of Ang II or norepinephrine on PAI-1 expression in wild type (WT) and Ang type-1a receptor knockout mice (AT1a-/-) in the presence or absence of the non-specific AT1 antagonist losartan. Ang II and norepinephrine increased systolic blood pressure equally, whereas losartan decreased the pressor response of the former but not the latter in WT mice. In AT1a-/- mice, baseline systolic blood pressure was lower with no effect of Ang II, norepinephrine, or losartan. Ang II stimulated PAI-1 expression in the heart, aorta, and kidney and markedly in the liver of WT mice. In AT1a-/- mice, Ang II-stimulated PAI-1 was significantly attenuated compared with the WT in the heart and aorta but significantly enhanced in the kidney. Losartan decreased the induction in the aorta and liver of WT, and in the kidney and liver of AT1a-/- mice. Norepinephrine increased PAI-1 expression in WT heart and aorta, and in AT1a-/- heart, kidney, and liver with no effect of losartan. Renal PAI-1 expression correlated with AT1b receptor mRNA. We conclude that Ang II stimulates PAI-1 expression in part through the AT1b receptor in the kidney and liver. Further, norepinephrine induces PAI-1 expression in vivo with AT1a receptor deficiency modulating the effect.
KW - Aldosterone
KW - Angiotensin
KW - Norepinephrine
KW - Plasminogen activator inhibitor-1
UR - http://www.scopus.com/inward/record.url?scp=34347334552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34347334552&partnerID=8YFLogxK
U2 - 10.1038/sj.ki.5002268
DO - 10.1038/sj.ki.5002268
M3 - Article
C2 - 17429342
AN - SCOPUS:34347334552
SN - 0085-2538
VL - 72
SP - 72
EP - 81
JO - Kidney international
JF - Kidney international
IS - 1
ER -