title: Participation of cyclooxygenase pathway in the vasoconstriction induced by 5-HT in the in situ autoperfused kidney of long-term diabetic rats.
abstract: We attempted to characterize the 5-hydroxytryptamine (5-HT) receptor type/subtype and mediator mechanisms involved in the contractile effects of 5-HT in the in situ autoperfused kidney of long-term diabetic rats. Diabetes was induced in male Wistar rats by a single subcutaneous injection of alloxan. Intra-arterial (i.a.) bolus injection of 5-HT (0.00000125 to 0.1μg/kg) increased renal perfusion pressure in a dose dependent way but did not affect the systemic blood pressure in long-term diabetic rats. The selective 5-HT2 receptor agonist, α-methyl-5-HT, caused a local vasoconstrictor effect in the in situ autoperfused rat kidney similar to 5-HT. However, BW723C86, a selective 5-HT2B receptor agonist, m-CPP (1-(3-chlorophenyl)piperazine), a selective 5-HT2B/2C receptor agonist, the 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), and the selective 5-HT3 receptor agonist, 1-phenylbiguanide did not modify the renal perfusion pressure. In long-term diabetic rats, vasoconstriction elicited by 5-HT and α-methyl-5-HT was significantly decreased by ritanserin (a 5-HT2 receptor antagonist), spiperone (a 5-HT2A receptor antagonist), and the cyclooxygenase (COX) inhibitors, indomethacin (non-selective COX inhibitor), FR 122047 or nimesulide (selective COX-1 and COX-2 inhibitors, respectively), but was not modified by pretreatment with SB 206553 (3,5-dihydro-5-methyl-N-3-pyridinylbenzo[1,2.b:4,5-b']dipyrrole(1H)-carboxamide hydrochloride), a non-selective 5-HT2C receptor antagonist, prazosin, propranolol, enalapril or losartan. The results of protein expression support these results: COX-1 and COX-2 are expressed in renal tissue. Inducible COX (COX-2) is overexpressed in long-term diabetes. Our data suggest that, in the in-situ autoperfused kidney of long-term diabetic rats, 5-HT vasoconstrictor action is mediated, through cyclooxygenase pathway, by local activation of 5-HT2A receptors.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Grupo de Enfermedades Cardiovasculares y Metabólicas, Facultad Ciencias de la Salud, Universidad del Quindío, Armenia, Colombia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Restrepo
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García
authors.affiliation: Departamento de Fisiología y Farmacología, Instituto "Reina Sofía" de investigación Nefrológica, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Barbero
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Luis San
authors.initials: LS
authors.lastname: Román
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martin
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Morán
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D011451:Prostaglandin-Endoperoxide Synthases