title: Mechanism of action of the cisapride-induced vasodilatation in renal vasculature of rat.
abstract: OBJECTIVE
  Cisapride is a prokinetic agent with cholinomimetic and 5-HT4 receptor agonistic properties. It has been proposed that cisapride-induced hypotension is partly mediated by cholinergic system. The aim of this study was to investigate the mechanism of cisapride-induced dilatation in the rat isolated perfused kidney.
  
  
  METHODS
  Left kidneys of Wistar rats were isolated and perfused via renal artery and the perfusion pressure was recorded. Cisapride given as bolus injections (10(-10)-3x10(-5) mol/l) produced dose-dependent dilatations. Perfusion of antagonists or inhibitors was started 30min before the onset of phenylephrine perfusion.
  
  
  RESULTS
  4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; blocker of M1, and M3 muscarinic receptors; 10(-7) mol/l) inhibited the responses to the lower doses of cisapride while, dextran (10(-7) mol/l), glibenclamide (inhibitor of ATP-sensitive potassium channels; 10(-5) mol/l) and capsaicin (for neuromediator depletion; 10(-6) mol/l) inhibited those to the higher doses. Dilatations induced by most of the doses of cisapride were inhibited by atropine (non-selective muscarinic receptor antagonist; 10(-7) mol/l), methylene blue (inhibitor of soluble guanylate cyclase; 10(-5) mol/l), 1H-[1,2,4] oxadiazolo-[4,3-a] Quinoxalin-1-One (ODQ; inhibitor of soluble guanylate cyclase; 10(-5) mol/l), and NG-nitro-L-arginine (L-NOARG; NO synthase inhibitor; 10(-4) mol/l). Inhibition induced by L-NOARG was reversed by L-arginine (10(-3) mol/l). The dilatation induced by cisapride was not affected by GR113808 (5-HT4 receptor antagonist; 10(-7) mol/l) and indomethacin (cyclooxygenase inhibitor; 10(-5) mol/l).
  
  
  CONCLUSIONS
  The findings indicated that cisapride caused vasodilatation through the release of nitric oxide (NO) as a result of the release of a substance acting on muscarinic receptors, in the renal vascular bed of the rat. The role of 5-HT4 receptors and prostanoids seemed unlikely.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Hacettepe, Sihhiye 06100, Ankara, Turkey.
authors.forename: Ender
authors.initials: E
authors.lastname: Tekes
authors.forename: Banu
authors.initials: B
authors.lastname: Bayar
authors.forename: Selda
authors.initials: S
authors.lastname: Emre-Aydingoz
authors.forename: Meral
authors.initials: M
authors.lastname: Tuncer
mesh_terms: D000818:Animals; D020117:Cisapride / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014664:Vasodilation
chemical_list: D017366:Serotonin Receptor Agonists; D020117:Cisapride