The importance of the endothelial nitric oxide synthase on the release of 6-nitrodopamine from mouse isolated atria and ventricles and their role on chronotropism

Autor(es)

Britto, Jose ; do Prado, Gustavo L. Pereira ; Chiavegatto, Silvana ; Cunha, Fernando ; Moraes, Manoel Odorico ; Moraes, Maria Elisabete A. ; Monica, Fabiola Z. ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 138, p. 8-pg., 2023-06-12.

Resumo

6-nitrodopamine (6-ND) is released from rat isolated atria, where it acts as a potent positive chronotropic agent. The release of 6-ND from rat isolated atria and ventricles is significantly reduced when pre-incubated with LNAME, and the release was not affected by tetrodotoxin pre-treatment, indicating that in the heart, the origin of 6-ND is not neurogenic. Since L-NAME inhibits all three isoforms of NO synthase, it was investigated the basal release of 6-ND from isolated atria and ventricles from nNOS-/- , iNOS-/- and eNOS-/- mice of either sex. The release of 6-ND was measured by LC-MS/MS. There were no significant differences in the 6-ND basal release from isolated atria and ventricles from male control mice, as compared to female control mice. The 6-ND release from atria obtained from eNOS-/- mice was significantly reduced when compared to atria obtained from control mice. The 6-ND release in nNOS-/- mice was not significantly different compared to control animals whereas the 6-ND release from atria obtained from iNOS- /-mice was significantly higher when compared to control group. Incubation of the isolated atria with LNAME caused a significant decrease in the basal atrial rate of control, nNOS-/-, and iNOS-/- mice, but not in eNOS- /- mice. The results clearly indicate that eNOS is the isoform responsible for the synthesis of 6-ND in the mice isolated atria and ventricles and supports the concept that 6-ND is the major mechanism by which endogenous NO modulates heart rate. (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
• Processo FAPESP: 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais
• Beneficiário: Gilberto de Nucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/14414-8 - Avaliação da ação das nitro-catecolaminas no sistema cardiovascular
• Beneficiário: José Britto Júnior
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado