title: Anticontractile activity of perivascular fat in obese mice and the effect of long-term treatment with melatonin.
abstract: OBJECTIVE
  It has been demonstrated previously that inflammation in perivascular adipose tissue (PVAT) may be implicated in vascular dysfunction. The aim of this study was to investigate the functional responses of small mesenteric arteries in a hyperphagic animal model of obesity after chronic treatment with melatonin, an endogenous hormone with antioxidant and vasculoprotective properties.
  
  
  RESULTS
  Ten obese mice (ob/ob) and 10 control lean mice (CLM) were treated with melatonin 100  mg/kg per day in the drinking water for 8 weeks. Mesenteric small resistance arteries were dissected and mounted on a wire myograph and a concentration-response to norepinephrine was evaluated in vessels with intact PVAT and after PVAT was removed and in the presence of iberiotoxin, a selective blocker of BKCA channels as well as under conditions of induced hypoxia in vitro. The presence of PVAT reduced the contractile response to norepinephrine in both ob/ob and CLM; however, the effect was significantly reduced in ob/ob. The anticontractile effect of PVAT completely disappeared with iberiotoxin preincubation. After melatonin treatment, inflammation was significantly ameliorated, and the contractile response in ob/ob and CLM was significantly reduced when PVAT was removed. Anticontractile effect of PVAT that is lost in obesity can be rescued using melatonin. A reduced expression of adiponectin and adiponectin receptor was observed in perivascular fat of ob/ob, whereas significant increase was observed in ob/ob treated with melatonin.
  
  
  CONCLUSIONS
  Melatonin seems to exert a protective effect on arteries from both ob/ob and CLM, counteracting the adverse effect of hypoxia and iberiotoxin.
authors.affiliation: aClinica Medica, Department of Clinical and Experimental Sciences bDepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy cFaculty of Medicine and Health Sciences, Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agabiti-Rosei
authors.forename: Carolina
authors.initials: C
authors.lastname: De Ciuceis
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossini
authors.forename: Enzo
authors.initials: E
authors.lastname: Porteri
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Rodella
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti-Rosei
authors.forename: Damiano
authors.initials: D
authors.lastname: Rizzoni
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001835:Body Weight; D000860:Hypoxia / Q000473:pathology; D007249:Inflammation; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D008856:Microscopy, Fluorescence; D009638:Norepinephrine / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress; D010455:Peptides / Q000494:pharmacology; D054419:Receptors, Adiponectin / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D052242:Adiponectin; D000975:Antioxidants; D010455:Peptides; D054419:Receptors, Adiponectin; C064719:iberiotoxin; D008550:Melatonin; D009638:Norepinephrine