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Hyperosmotic evoked sympathoexcitation is blocked by overexpression of macrophage inhibitory migration factor (MIF) in the paraventricular nucleus of hypothalamus (PVN)
Author(s) -
Colombari Eduardo,
Colombari Debora Simoes Almeida,
Li Hongwei,
Sumners Colin,
Raizada Mohan K,
Murphy David,
Paton Julian F. R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.792.11
Subject(s) - macrophage migration inhibitory factor , hypothalamus , medicine , inhibitory postsynaptic potential , endocrinology , saline , chemistry , receptor , osmotic concentration , stimulation , homeostasis , cytokine
In anaesthetized rats, systemic hyperosmotic stimulation (HS) evokes increases in sympathetic nerve activity (SNA) that are mediated by activation of AT 1 receptors in the PVN. Further, MIF can antagonize ANG II‐induced cardiovascular effects mediated via the PVN. This inhibitory effect of MIF is due to its intrinsic thiol‐protein oxidoredutase (TPOR) activity. In this study, we evaluated the effect of overexpressing either MIF or C60SMIF (which lacks TPOR activity) in the PVN on the sympathoexcitation induced by HS. Male Wistar rats (65‐85 g) were decorticated to make insentient and perfused intra‐arterially. HS was performed by raising the perfusate osmolality from 290 to 380 mOsmol for 40 s. Adeno associated 2 viruses for over expression of MIF (1.0x 10 8 ), C60SMIF (1.0x 10 8 ) or eGFP (8.3 x 10 8 ) were injected bilaterally (500 nl/side) into the PVN as was saline as a control. Seven to 10 days later the HS‐induced sympathoexcitation in both the saline and eGFP groups (increases of 27 ± 4 and 25 ± 4%, respectively) was not observed in the MIF group (4 ± 5%). Conversely, the HS induced SNA response was potentiated (45 ± 6%) in the C60SMIF group. We propose that MIF is a major counter regulator of HS induced sympathoexcitation, which is dependent on its TPOR activity. Further, manipulation of TPOR may have therapeutic potential in restricting salt‐induced hypertension. Funded by CNPq (Brazil), CAPES (Brazil), The Royal Society.