title: Long-term neuropeptide Y administration in the periphery induces abnormal baroreflex sensitivity and obesity in rats.
abstract: Neuropeptide Y (NPY) is an important neuronal element involved in cardiovascular regulation. Since elevated plasma levels of NPY have been observed in numerous pathological situations, this study aimed to determine whether long-term elevated plasma concentrations of NPY could result in aberrant baroreflex sensitivity. Mini-osmotic pump containing NPY (85 μg per 30 days) was subcutaneously implanted between scapulae in male rats for 4 months. The rats treated with NPY showed the following characters compared with control group: (1) attenuated heart rate responding to the increases in mean arterial blood pressure (MABP) induced by phenylephrine, but enhanced heart rate responding to the decreases in MABP induced by sodium nitroprusside; (2) decreased protein levels of substance P (SP) and GluR2, while increased the expression of γ-aminobutyric acid A receptor (GABA(A)R) in brainstem; (3) abdominal obesity indicated by increased body weight and accumulated fat mass in peritoneal cavity; (4) significant increases in total cholesterol, triglycerides, and low density lipoprotein levels in the periphery. These findings indicate that long-term NPY administration in the periphery leads to abnormal baroreflex sensitivity due, at least in part, to the down-regulated expression of SP/GluR2 and elevated expression of GABA(A)R in both protein and RNA levels, which indicate the alternations in glutamate function and GABA action in the nucleus tractus solitarii in NPY-treated rats. Furthermore, long-term NPY administration results in abdominal obesity and dyslipidemia.
authors.affiliation: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratory of Biomedicine-Pharmaceutics of China), Harbin, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Luyao
authors.initials: L
authors.lastname: Sun
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D008077:Lipoproteins, LDL; D009478:Neuropeptide Y; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D014280:Triglycerides; D009599:Nitroprusside; D013373:Substance P; D002784:Cholesterol; C104722:glutamate receptor ionotropic, AMPA 2