| Full text | |
| Author(s): |
Britto-Junior, Jose
;
Campos, Rafael
;
Peixoto, Matheus
;
Lima, Antonio Tiago
;
Jacintho, Felipe Fernandes
;
Monica, Fabiola Z.
;
Moreno, Ronilson Agnaldo
;
Antunes, Edson
;
De Nucci, Gilberto
Total Authors: 9
|
| Document type: | Journal article |
| Source: | COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 260, p. 7-pg., 2022-07-07. |
| Abstract | |
Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 mu M) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 mu M) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA(2) 6.09) and L-NAME pre-treated endothelium-intact (pA(2) 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 mu M). In the thromboxane A(2) mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 mu M) and the dopamine D-2-receptor antagonist haloperidol (1 nM-1 mu M) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D-2-like receptor antagonist. (AU) | |
| FAPESP's process: | 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines |
| Grantee: | Gilberto de Nucci |
| Support Opportunities: | Research Projects - Thematic Grants |
| 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 |
| FAPESP's process: | 18/24971-9 - Physiological relevance of catecholamines produced by the endothelium |
| Grantee: | Felipe Fernandes Jacintho |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats |
| Grantee: | Antonio Tiago Silva Lima |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |