| Full text | |
| Author(s): |
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]
Total Authors: 7
|
| Affiliation: | [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
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Life Sciences; v. 276, JUL 1 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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) | |
| FAPESP's process: | 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate |
| Grantee: | Edson Antunes |
| Support Opportunities: | Research Projects - Thematic Grants |