Mechanism of action of the cisapride-induced vasodilatation in renal vasculature of rat.
| Autor: | Tekes E; Department of Pharmacology, Faculty of Medicine, University of Hacettepe, Sihhiye 06100, Ankara, Turkey., Bayar B, Emre-Aydingoz S, Tuncer M |
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| Jazyk: | angličtina |
| Zdroj: | The Indian journal of medical research [Indian J Med Res] 2004 Mar; Vol. 119 (3), pp. 115-20. |
| Abstrakt: | Background & Objectives: 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). Interpretation & Conclusion: 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. |
| Databáze: | MEDLINE |
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