title: Globular and full-length adiponectin induce NO-dependent vasodilation in resistance arteries of Zucker lean but not Zucker diabetic fatty rats.
abstract: BACKGROUND
  Adiponectin increases nitric oxide (NO) production in endothelial cell cultures and is reduced in the circulation of obese and diabetic patients, but its functional effect on resistance arteries is not yet studied in detail.
  
  
  METHODS
  We assessed the direct vasodilatory response of isolated mesenteric resistance arteries of Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats to globular adiponectin (gAd) and full-length adiponectin (fAd) and tested the effect of additional reactive oxygen species (ROS) inhibitors in vitro. Serum adiponectin and insulin levels were measured by ELISA. The mRNA expressions of the adiponectin receptors and the downstream signaling molecules adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1), adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2 (APPL2), and endothelial NO synthase (eNOS) in mesenteric resistance arteries were quantified by real-time reverse transcriptase PCR.
  
  
  RESULTS
  Both gAd and fAd induced a relevant dose-dependent vasodilation in ZL, but not in hypoadiponectinemic ZDF rats. This effect was totally blunted by L-nitroarginine-methyl-ester indicating NO dependency. The addition of ROS inhibitors could not improve the vasodilatory effect of adiponectin. Vasodilatory response to acetylcholine was reduced in ZDF rats, which could not be enhanced by low-dose adiponectin. Adiponectin receptor 1 (AdipoR1) was higher expressed than adiponectin receptor 2 (AdipoR2) with no significant differences between both animal groups, but APPL1 was significantly decreased in ZDF rats. The eNOS expression was not significantly different between ZL and ZDF rats.
  
  
  CONCLUSIONS
  Adiponectin exerts a NO-dependent vasodilation in resistance arteries of normoglycemic ZL rats, but not diabetic ZDF rats. This may contribute to endothelial dysfunction in ZDF rats. Alterations in the expression of APPL1 may be involved in the observed insensitivity to adiponectin in ZDF rats.
authors.affiliation: Klinik und Poliklinik für Innere Medizin, University of Regensburg, Germany. peterm.schmid@klinik.uni-regensburg.de
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schmid
authors.forename: Markus
authors.initials: M
authors.lastname: Resch
authors.forename: Andreas
authors.initials: A
authors.lastname: Steege
authors.forename: Sabine
authors.initials: S
authors.lastname: Fredersdorf-Hahn
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stoelcker
authors.forename: Christoph
authors.initials: C
authors.lastname: Birner
authors.forename: Christian
authors.initials: C
authors.lastname: Schach
authors.forename: Christa
authors.initials: C
authors.lastname: Buechler
authors.forename: Guenter A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: Andreas
authors.initials: A
authors.lastname: Luchner
authors.forename: Dierk H
authors.initials: DH
authors.lastname: Endemann
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness / Q000503:physiopathology*; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; C515694:Appl1 protein, rat; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine