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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

6-Nitrodopamine is released by human umbilical cord vessels and modulates vascular reactivity

Texto completo
Autor(es):
Britto-Junior, Jose [1] ; Coelho-Silva, Weverton C. [1] ; Murari, Guilherme Figueiredo [1] ; Serpellone Nash, Charles Elliot [1] ; Monica, Fabiola Z. [1] ; Antunes, Edson [1] ; De Nucci, Gilberto [2, 1, 3]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] State Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas, SP - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[3] Univ Brasil, Fac Med Sci, Fernandopolis, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Life Sciences; v. 276, JUL 1 2021.
Citações Web of Science: 0
Resumo

Aims: Human umbilical cord vessels (HUCV) release dopamine and nitric oxide (NO). This study aims to verify whether HUCV release nitrocatecholamines such as 6-nitrodopamine (6-ND). Main methods: Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to identify 6ND release from HUCV rings incubated in Krebs-Henseileit?s solution. Vascular reactivity of HUCV rings was tested (with and without endothelium integrity) by suspension of the rings in an organ bath under isometric tension and application of 6-ND and other known mediators. Key findings: LC-MS/MS revealed a basal release of 6-ND from endothelium intact from both human umbilical artery (HUA) and vein (HUV). The endothelium intact release was inhibited by the pre-treatment with NO synthesis inhibitor L-NAME (100 ?M). In contrast to dopamine, noradrenaline and adrenaline, 6-ND did not contract HUCV, even in presence of L-NAME or ODQ. 6-ND (10 ?M) produced a rightward shift of the concentration-response curves to dopamine (pA2: 5.96 in HUA and 5.72 in HUV). Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND (10 ?M). In U-46619 (10 nM) pre-contracted endothelium intact tissues, 6-ND and the dopamine D2-receptor antagonist haloperidol induced concentration-dependent relaxations of HUA and HUV. Incubation with the dopamine D1receptor antagonist SCH-23390 (10 nM) abolished relaxation induced by fenoldopam but did not affect those induced by 6-ND. Significance: 6-ND is released by HUCV and acts as a selective dopamine D2-receptor antagonist in this tissue. This represents a novel mechanism by which NO may modulate vascular reactivity independently of cGMP production. (AU)

Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
Beneficiário:Edson Antunes
Modalidade de apoio: Auxílio à Pesquisa - Temático