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Eur J Pharmacol. 2011 May 20;659(1):37-44. doi: 10.1016/j.ejphar.2011.03.006. Epub 2011 Mar 22.

Participation of cyclooxygenase pathway in the vasoconstriction induced by 5-HT in the in situ autoperfused kidney of long-term diabetic rats.

Author information

1
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.
2
Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
3
Departamento de Fisiología y Farmacología, Instituto "Reina Sofía" de investigación Nefrológica, Universidad de Salamanca, 37007 Salamanca, Spain.

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.

PMID:
21414306
DOI:
10.1016/j.ejphar.2011.03.006
[Indexed for MEDLINE]

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