title: Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress.
abstract: Macrophage migration inhibitory factor (MIF) counteracts pressor effects of angiotensin II (ANG II) in the paraventricular nucleus of the hypothalamus (PVN) in normotensive rats, but this mechanism is absent in spontaneously hypertensive rats (SHRs) due to a lack of MIF in PVN neurons. Since endogenous ANG II in the PVN modulates stress reactivity, we tested the hypothesis that replacement of MIF in PVN neurons would reduce baseline blood pressure and inhibit stress-induced increases in blood pressure and plasma corticosterone in adult male SHRs. Radiotelemetry transmitters were implanted to measure blood pressure, and then an adeno-associated viral vector expressing either enhanced green fluorescent protein (GFP) or MIF was injected bilaterally into the PVN. Cardiovascular responses to a 15-min water stress (1-cm deep, 25°C) and a 60-min restraint stress were evaluated 3-4 wk later. MIF treatment in the PVN attenuated average restraint-induced increases in blood pressure (37.4 ± 2.0 and 27.6 ± 3.5 mmHg in GFP and MIF groups, respectively, P < 0.05) and corticosterone (42 ± 2 and 36 ± 3 μg/dl in GFP and MIF groups, respectively, P < 0.05). MIF treatment in the PVN also reduced stress-induced elevations in the number of c-Fos-positive cells in the rostral ventrolateral medulla (71 ± 5 in GFP and 47 ± 5 in MIF SHRs, P < 0.01) and corticotropin-releasing factor mRNA expression in the PVN. However, MIF had no significant effects on the cardiovascular responses to water stress in SHRs or to either stress in Sprague-Dawley rats. Therefore, viral vector-mediated restoration of MIF in PVN neurons of SHRs attenuates blood pressure and hypothalamic pituitary adrenal axis responses to stress.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Benedek
authors.identifier: http://orcid.org/0000-0002-9074-2491
authors.initials: B
authors.lastname: Erdos
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Rebekah R
authors.initials: RR
authors.lastname: Clifton
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Michael L
authors.initials: ML
authors.lastname: McCowan
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida scheuerd@ufl.edu.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Scheuer
mesh_terms: D000818:Animals; D001794:Blood Pressure; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat
keywords: angiotensin ii; blood pressure; brain; hypertension; psychological stress