title: Adiponectin-induced dilation of isolated porcine retinal arterioles via production of nitric oxide from endothelial cells.
abstract: OBJECTIVE
  Adiponectin, an important adipocytokine secreted by adipocytes, has anti-inflammatory and atheroprotective effects on vascular tissue via the adiponectin receptor (adipoR). However, the action of adiponectin in the retinal microcirculation is unknown. We examined the direct effect and underlying mechanism of the vasomotor action of adiponectin in porcine retinal arterioles.
  
  
  METHODS
  Porcine retinal arterioles (internal diameter, 60-90 μm) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record changes in diameter in response to adiponectin.
  
  
  RESULTS
  The retinal arterioles dilated in a dose-dependent (0.125-7.5 μg/mL) manner in response to adiponectin. The vasodilation decreased significantly after removal of the endothelium. N(G)-nitro-L-arginine methyl ester (a nitric oxide [NO] synthase inhibitor), 1H-1,2,4-oxadia-zolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), but not wortmannin (a phosphatidylinositol 3-kinase inhibitor) inhibited the effect of adiponectin-induced vasodilation comparable with that of denudation. Pretreatment with compound C, an activated protein kinase (AMPK) inhibitor, partially but significantly reduced vasodilation. Incubation with GW6471, a peroxisome proliferator-activated receptor blocker, did not significantly inhibit vasodilation by adiponectin. AdipoR1 and adipoR2 immunoreactions were observed in the endothelium of retinal arterioles.
  
  
  CONCLUSIONS
  Adiponectin elicits mainly endothelium-dependent dilation of the retinal arterioles. Endothelium-dependent vasodilation likely induced by adiponectin results from NO via activation of guanylyl cyclase that is partially dependent on AMPK activity. Understanding the effect of adiponectin on the retinal vasculature may help improve potential therapies for retinal vascular disorders, especially diabetic retinopathy in patients with type 2 diabetes mellitus.
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Omae
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tanano
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003930:Diabetic Retinopathy / Q000188:drug therapy; D004728:Endothelium, Corneal / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: adiponectin; endothelial cells; nitric oxide; oxidative stress; retinal circulation