title: Leptin-induced endothelial dysfunction is mediated by sympathetic nervous system activity.
abstract: BACKGROUND
  The adipocyte-derived hormone leptin is elevated in obesity and may contribute to vascular risk associated with obesity. The mechanism(s) by which leptin affects vascular disease is unclear, although leptin has been shown to increase sympathetic activity. The aim of this study was to investigate the effect of leptin treatment on endothelial function and the role of the local sympathetic nervous system in mediating these effects.
  
  
  RESULTS
  Recombinant leptin was administered to C57BL6/J mice every other day for 1 week. Mesenteric arteriole myography revealed that leptin treatment caused significant impairment of endothelium-dependent vasorelaxation. Although leptin alone did not raise aortic blood pressure, leptin treatment augmented the blood pressure response to angiotensin II. The effects of leptin on mesenteric arteriolar function and aortic blood pressure response to angiotensin II were neutralized following sympathetic denervation to the mesenteric vasculature. The superoxide scavenger TEMPOL was also effective in preventing the effects of leptin on endothelial dysfunction.
  
  
  CONCLUSIONS
  Leptin causes endothelial dysfunction and enhances the effects of angiotensin II on blood pressure. These effects of leptin are mediated by sympathetic nervous system activation and superoxide and may contribute to vascular stiffness and hypertension in obesity.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, Ann Arbor, MI.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Chiao
authors.initials: C
authors.lastname: Guo
authors.forename: Julia
authors.initials: J
authors.lastname: Wang
authors.forename: Y E
authors.initials: YE
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Chang
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D020738:Leptin
keywords: ganglionectomy; hypertension; nervous system; obesity; superoxide
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