title: Blockade of Salusin-β in Hypothalamic Paraventricular Nucleus Attenuates Hypertension and Cardiac Hypertrophy in Salt-induced Hypertensive Rats.
abstract: Salusin-β, a multifunctional bioactive peptide, is considered as a promising candidate biomarker for predicting cardiovascular diseases. This study was designed to determine whether inhibition of salusin-β in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by restoring neurotransmitters and cytokines. Male Sprague Dawley rats were fed with a normal salt diet (NS, 0.3%) or a high salt diet (HS, 8%) for 8 weeks to induce hypertension. Then, these rats received bilateral PVN infusion of a specific salusin-β blocker, antisalusin-β IgG (SIgG), or control IgG (CIgG) for 2 weeks. HS rats exhibited higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/bodyweight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and messenger RNA levels of cardiac atrial natriuretic peptide (ANP), and β-myosin heavy chain. Compared with NS rats, HS rats had higher levels of glutamate, norepinephrine, tyrosine hydroxylase, proinflammatory cytokines, and lower levels of gamma-aminobutyric acid, interleukin 10, and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN, and higher plasma levels of proinflammatory cytokines. Chronic PVN infusion of SIgG attenuated all these changes in HS rats. Our findings suggest that HS rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between proinflammatory and anti-inflammatory cytokines in the PVN; and chronic inhibition of salusin-β in the PVN restores neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive responses and cardiac hypertrophy.
authors.affiliation: *Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an, China; †Department of Physiology, Shantou University Medical College, Shantou, China; ‡Department of Obstetrics and Gynecology, Shanxi Provincial People's Hospital, Taiyuan, China; §Department of Public Health, Xi'an Jiaotong University School of Public Health, Xi'an, China; ¶Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; ‖Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; and **Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Hong-Bao
authors.initials: HB
authors.lastname: Li
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Qin
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Suo
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.forename: Yu-Wang
authors.initials: YW
authors.lastname: Miao
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Sun
authors.forename: Qiu-Yue
authors.initials: QY
authors.lastname: Yi
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D018377:Neurotransmitter Agents; D017673:Sodium Chloride, Dietary; C528274:salusin-beta, rat