Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency

N. J. Brown*, J. Bradford, Z. Wang, W. Lea, L. Ma, J. Ma, D. E. Vaughan, A. B. Fogo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalKidney international
Volume72
Issue number1
DOIs
StatePublished - Jul 2007

Keywords

  • Aldosterone
  • Angiotensin
  • Norepinephrine
  • Plasminogen activator inhibitor-1

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT<sub>1a</sub> receptor deficiency'. Together they form a unique fingerprint.

Cite this