title: Rosiglitazone reverses increased duodenal inhibitory response in spontaneously hypertensive rats.
abstract: BACKGROUND
  Thiazolidinediones (TZDs) including rosiglitazone (ROSI) are insulin sensitizing agents with beneficial gastrointestinal effects. However, no studies are available on TZDs effect in gastrointestinal motility. We evaluated the effects of ROSI on gastrointestinal inhibitory neurotransmission focusing on the modulatory roles of nitric oxide synthase/nitric oxide (NOS/NO) and heme oxygenase/carbon monoxide (HO/CO) pathways.
  
  
  METHODS
  Spontaneously hypertensive rats (SHR) were used as model of insulin resistance. Duodenal strips were obtained from vehicle-treated SHR, ROSI-treated SHR (5 mg kg(-1) by gavage daily per 6 weeks), and Wistar Kyoto (WKY). Inhibitory responses to electrical field stimulation (EFS) were evaluated in the presence of HO inhibitor zinc protoporphyrin IX (ZnPPIX, 10 μmol L(-1)) or NOS inhibitor N(G)-nitro-L-arginine (L-NNA, 100 μmol L(-1)), alone and in combination. Protein levels of HO and NOS isoforms were evaluated by immunohistochemistry and western blot analysis.
  
  
  RESULTS
  Basal responses to EFS were significantly increased in duodenum strips from vehicle-treated SHR vs WKY. This effect was reversed in ROSI-treated SHR. The EFS-mediated relaxation was comparably reduced by ZnPPIX in WKY and SHR, but not in ROSI-treated SHR animals. The L-NNA reduced EFS response to a similar extent in WKY and ROSI -treated SHR, but its effect was significantly higher in vehicle-treated SHR. Expression of HO-1 protein was significantly lower, whereas HO-2 protein levels were unchanged in ROSI-treated SHR with respect to vehicle-treated SHR. Finally, increased levels of nNOS in vehicle-treated SHR were reduced in ROSI-treated SHR.
  
  
  CONCLUSIONS
  Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components.
authors: Department of Biomedical Sciences and Human Oncology, Medical School, University of Bari Aldo Moro, Bari, Italy.
authors: L
authors: L
authors: De Benedictis
authors: M A
authors: MA
authors: Potenza
authors: S
authors: S
authors: Gagliardi
authors: A
authors: A
authors: Zigrino
authors: M
authors: M
authors: Montagnani
authors: M A
authors: MA
authors: De Salvia
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D007527:Isoenzymes; D011524:Protoporphyrins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing)