Macrophage migration inhibitory factor in the paraventricular nucleus plays a major role in the sympathoexcitatory response to salt

E Colombari, D S A Colombari, H Li, P Shi, Y Dong, N Jiang, M K Raizada, C Sumners, D Murphy, JFR Paton

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

Abstract

Central hyperosmotic stimulation (HS) evokes increases in sympathetic nerve activity mediated by activation of angiotensin type 1 receptors in the hypothalamic paraventricular nucleus (PVN). Macrophage inhibitory migration factor (MIF) is an intracellular inhibitory regulator of angiotensin type 1 receptor–mediated actions of angiotensin II within neurons of the PVN. MIF mediates its actions via its intrinsic thiol-protein oxidoreductase activity. We demonstrate that intracerebroventricular injection of hypertonic saline into Sprague-Dawley rats elicits a significant (≈112%) increase in MIF mRNA expression in the PVN. Next, we evaluated the effect of viral-mediated expression of either MIF or [C60S]-MIF (which lacks thiol-protein oxidoreductase activity) in the PVN on the sympathoexcitation evoked by HS. We used a decorticate, arterially perfused in situ preparation of male Wistar rats (60 to 80 g). HS was induced by raising perfusate osmolality from 290 to 380 milliosmoles for 40 seconds. Seven to 10 days before experiments, rats were injected bilaterally (500 nL per side) with 0.9% saline (control) or with adenoassociated virus to express MIF, [C60S]-MIF, or enhanced green fluorescent protein in the PVN. HS produced sympathoexcitation in both the 0.9% saline and enhanced green fluorescent protein groups (sympathetic nerve activity increase of +27±4% and +25±4%, respectively; P
Translated title of the contributionMacrophage migration inhibitory factor in the paraventricular nucleus plays a major role in the sympathoexcitatory response to salt
Original languageEnglish
Pages (from-to)956 - 963
Number of pages8
JournalHypertension
Volume56
Issue number5
Early online date11 Oct 2010
DOIs
Publication statusPublished - Nov 2010

Fingerprint Dive into the research topics of 'Macrophage migration inhibitory factor in the paraventricular nucleus plays a major role in the sympathoexcitatory response to salt'. Together they form a unique fingerprint.

Cite this