Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria

Autor(es)

Britto-Junior, Jose ; Lima, Antonio Tiago ; Fuguhara, Vivian ; Monica, Fabiola Z. Z. ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. N/A, p. 12-pg., 2023-01-31.

Resumo

6-Nitrodopamine (6-ND) is released from rat isolated atria being 100 times more potent than noradrenaline and adrenaline, and 10,000 times more potent than dopamine as a positive chronotropic agent. The present study aimed to investigate the interactions of 6-ND with the classical catecholamines, phosphodiesterase (PDE)-3 and PDE4, and the protein kinase A in rat isolated atria. Atrial incubation with 1 pM of dopamine, noradrenaline, or adrenaline had no effect on atrial frequency. Similar results were observed when the atria were incubated with 0.01 pM of 6-ND. However, co-incubation of 6-ND (0.01 pM) with dopamine, noradrenaline, or adrenaline (1 pM each) resulted in significant increases in atrial rate, which persisted over 30 min after washout of the agonists. The increased atrial frequency induced by co-incubation of 6-ND with the catecholamines was significantly reduced by the voltage-gated sodium channel blocker tetrodotoxin (1 mu M, 30 min), indicating that the positive chronotropic effect of 6-ND is due in part to activation of nerve terminals. Pre-treatment of the animals with reserpine had no effect on the positive chronotropic effect induced by dopamine, noradrenaline, or adrenaline; however, reserpine markedly reduced the 6-ND (1 pM)-induced positive chronotropic effect. Incubation of the rat isolated atria with the protein kinase A inhibitor H-89 (1 mu M, 30 min) abolished the increased atrial frequency induced by dopamine, noradrenaline, and adrenaline, but only attenuated the increases induced by 6-ND. 6-ND induces catecholamine release from adrenergic terminals and increases atrial frequency independently of PKA activation. (AU)

• 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: 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: 21/13593-6 - Avaliação do tratamento crônico da 6-nitrodopamina em ratos
• Beneficiário: Antonio Tiago Silva Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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
• Processo FAPESP: 22/07737-8 - Avaliação do efeito cardiovascular da 6-nitrodopamina em átrio isolado e coração perfundido de rato
• Beneficiário: Vivian Fuguhara de Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto