| Alosetron, cilansetron and tegaserod modify mesenteric but not colonic blood flow in rats. | |
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MedLine Citation:
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PMID: 19785647 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: As the use of the 5-HT(3) receptor antagonist alosetron (GlaxoSmithKline) and the 5-HT(4) receptor agonist tegaserod (Novartis) in patients with irritable bowel syndrome has been associated with cases of ischaemic colitis, the effects of alosetron, cilansetron (Solvay) and tegaserod on the rat splanchnic circulation were evaluated. EXPERIMENTAL APPROACH: Phenobarbital-anaesthetised rats were instrumented to record blood flow in the superior mesenteric artery and transverse colon and to calculate mesenteric and colonic vascular conductance. KEY RESULTS: Intravenous alosetron (0.03-0.3 mg.kg(-1)) did not alter blood pressure or heart rate but reduced mesenteric blood flow and vascular conductance by 15-20%. This activity profile was also seen after intraduodenal alosetron and shared by the 5-HT(3) receptor antagonist cilansetron. In contrast, blood flow, vascular conductance and intraluminal pressure in the colon were not modified by alosetron and cilansetron. Intravenous or intraduodenal tegaserod (0.3-1.0 mg.kg(-1)) had no inhibitory effect on mesenteric and colonic blood flow. Peroral treatment of rats with alosetron or tegaserod for 7 days did not modify mesenteric haemodynamics at baseline and after blockade of nitric oxide synthesis. Mild inflammation induced by dextran sulphate sodium failed to provoke a vasoconstrictor effect of cilansetron in the colon. CONCLUSIONS AND IMPLICATIONS: Alosetron and cilansetron, not tegaserod, caused a small and transient constriction of the rat mesenteric vascular bed, whereas blood flow in the colon remained unaltered. The relevance of these findings to the treatment-associated occurrence of ischaemic colitis in patients with irritable bowel syndrome remains open. |
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Authors:
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Evelin Painsipp; Anaid Shahbazian; Peter Holzer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-25 |
Journal Detail:
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Title: British journal of pharmacology Volume: 158 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-28 Completed Date: 2010-02-12 Revised Date: 2011-04-06 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1210-26 Citation Subset: IM |
Affiliation:
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Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic alpha-Agonists
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pharmacology Animals Blood Pressure / drug effects Carbazoles / administration & dosage, adverse effects* Carbolines / administration & dosage, adverse effects* Clonidine / pharmacology Colitis / physiopathology Colon / blood supply, drug effects* Fasting Female Heart Rate / drug effects Indoles / administration & dosage, adverse effects* Mesenteric Artery, Superior / drug effects, physiology NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase / antagonists & inhibitors Pyridines / administration & dosage, adverse effects* Rats Rats, Sprague-Dawley Regional Blood Flow / drug effects Serotonin 5-HT3 Receptor Antagonists* Serotonin 5-HT4 Receptor Antagonists* Splanchnic Circulation / drug effects* Vasoconstrictor Agents / pharmacology Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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L 25-B05//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-Agonists; 0/Carbazoles; 0/Carbolines; 0/Indoles; 0/Pyridines; 0/Serotonin 5-HT3 Receptor Antagonists; 0/Serotonin 5-HT4 Receptor Antagonists; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 120635-74-7/cilansetron; 122852-42-0/alosetron; 145158-71-0/tegaserod; 4205-90-7/Clonidine; 50903-99-6/NG-Nitroarginine Methyl Ester; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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