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

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• 作者：Beatriz Restrepo^a ; ^b ; Mó ; nica Garc&#xed ; a^a ; Alicia Rodr&#xed ; guez-Barbero^c ; Luis San Romá ; n^a ; Mar&#xed ; a Luisa Martin^a ; Asunció ; n Morá ; n^a ; ^{amoran@usal.es"" rel=""nofollow}
• 关键词：5-Hydroxytryptamine ; 5-HT_2A receptor ; Autoperfused rat kidney ; Long-term diabetes ; Cyclooxygenase pathway
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：20 May 2011
• 年：2011
• 卷：659
• 期：1
• 页码：37-44
• 全文大小：3282 K

文摘

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 0.1 μg/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-HT_2B receptor agonist, m-CPP (1-(3-chlorophenyl)piperazine), a selective 5-HT_2B/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-HT_2A 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-HT_2C 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-HT_2A receptors.