title: Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels.
abstract: OBJECTIVE
  Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, has been shown to exert cardiovascular benefits, but its action in the retinal microcirculation remains unknown. In this study, the direct effect and the underlying mechanism of the vasomotor action of resveratrol were examined in retinal arterioles.
  
  
  METHODS
  Porcine retinal arterioles were isolated, cannulated, and pressurized without flow for in vitro study. Resveratrol-induced diameter changes were recorded by videomicroscopic techniques.
  
  
  RESULTS
  Retinal arterioles (65 +/- 3 microm) dilated dose dependently in response to resveratrol (1-50 microM). The removal of the endothelium reduced this dilation by 50%. Inhibition of nitric oxide (NO) synthase (by L-NAME; N(G)-nitro-L-arginine methyl ester) and blockade of soluble guanylyl cyclase (by ODQ; 1H-1,2,4-oxadiazolo[4,3-a]quinoxalin-1-one) produced similar inhibition as that produced by denudation. However, the resveratrol response was not affected by indomethacin (a cyclooxygenase inhibitor) and sulfaphenazole (an epoxygenase inhibitor). Intraluminal administration of an extracellular signal-regulated kinase (ERK) inhibitor (PD98059), but not an estrogen receptor blocker (ICI 182780), also reduced vasodilation by 50%. A nonselective K(+) channel blocker, tetraethylammonium (TEA), and a large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor, iberiotoxin, produced identical inhibition of resveratrol-induced dilation. However, the dilation was insensitive to the inhibitors of ATP-sensitive K(+) channels and voltage-gated K(+) channels. Coadministration of L-NAME and iberiotoxin almost abolished the vasodilation induced by resveratrol.
  
  
  CONCLUSIONS
  Resveratrol elicits endothelium-dependent and -independent dilation of retinal arterioles. Endothelium-dependent dilation is mediated by the released NO, probably via NO synthase (NOS) activation by the ERK pathway and the subsequent activation of soluble guanylyl cyclase. The activation of BK(Ca) channels in smooth muscle contributes to the endothelium-independent dilation caused by resveratrol. A better understanding of the action of resveratrol on retinal vasculature may help shed light on its therapeutic potential for retinal vascular disease.
authors.affiliation: Department of Ophthalmology, Scott & White Eye Institute, College of Medicine, Texas A&M Health Science Center, Temple, TX 76504, USA. tnagaoka@medicine.tamhsc.edu
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Travis W
authors.initials: TW
authors.lastname: Hein
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Lih
authors.initials: L
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D000077185:Resveratrol; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014741:Video Recording; D014920:Wine
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000975:Antioxidants; D005419:Flavonoids; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011810:Quinoxalines; D013267:Stilbenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D000077185:Resveratrol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D019331:NG-Nitroarginine Methyl Ester