Macrophage migration inhibitory factor in the PVN attenuates the central pressor and dipsogenic actions of angiotensin II.
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.
Li
Hongwei
H
Department of Physiology and Functional Genomics and McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0274, USA.
Gao
Yongxin
Y
Freire
Carlos Diez
CD
Raizada
Mohan K
MK
Toney
Glenn M
GM
Sumners
Colin
C
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D018014:Gene Transfer Techniques; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology
D008263:Macrophage Migration-Inhibitory Factors; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II