Macrophage migration inhibitory factor in the PVN attenuates the central pressor and dipsogenic actions of angiotensin II

Hongwei Li, Yongxin Gao, Carlos Diez Freire, Mohan K. Raizada, Glenn M. Toney, Colin Sumners

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Macrophage migration inhibitory factor (MIF) acts intracellularly to counteract the angiotensin (ANG) II type 1 receptor (AT1-R)-mediated chronotropic effect of ANG II in hypothalamic neurons, an effect mediated by the thiol-protein oxidoreductase (TPOR) activity of the MIF molecule. Here we determined the in vivo actions of MIF in regulating the physiological actions of ANG II that are mediated via the paraventricular nucleus (PVN), an area that serves as a relay point in the central nervous system (CNS)-mediated effects of ANG II on cardiovascular functions and water intake. Intracerebroventricular (icv) injection of ANG II into normotensive rats selectively increased MIF protein levels in the PVN and produced significant pressor and drinking responses that were inhibited by PVN administration of the AT1-R antagonist losartan. Overexpression of MIF in PVN neurons via Ad-Syn-MIF gene transfer attenuated the pressor and drinking responses produced by icv-injected ANG II. Consistently, intracellular application of MIF or MIF-(50-65) (which harbors the TPOR activity of MIF) into PVN sympathetic regulatory neurons, blunted the electrophysiological actions of ANG II at these cells. These observations establish for the first time that MIF within the PVN, acting via TPOR, is an intracellular regulator of the central cardiovascular and dipsogenic effects of ANG II.

Original languageEnglish (US)
Pages (from-to)E1146-E1156
JournalFASEB Journal
Volume20
Issue number10
DOIs
StatePublished - Aug 2006

Keywords

  • ANG II
  • Blood pressure
  • Paraventricular nucleus
  • Thiol-protein oxidoreductase

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Macrophage migration inhibitory factor in the PVN attenuates the central pressor and dipsogenic actions of angiotensin II'. Together they form a unique fingerprint.

Cite this