Rosiglitazone reverses increased duodenal inhibitory response in spontaneously hypertensive rats
Article first published online: 14 OCT 2011
© 2011 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 1, pages e56–e66, January 2012
How to Cite
De Benedictis, L., Potenza, M. A., Gagliardi, S., Zigrino, A., Montagnani, M. and De Salvia, M. A. (2012), Rosiglitazone reverses increased duodenal inhibitory response in spontaneously hypertensive rats. Neurogastroenterology & Motility, 24: e56–e66. doi: 10.1111/j.1365-2982.2011.01798.x
- Issue published online: 21 DEC 2011
- Article first published online: 14 OCT 2011
- Received: 18 April 2011 Accepted for publication: 16 September 2011
- gastrointestinal motility;
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 NG-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.
Key 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 & Inferences Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components.