The pivotal role of neuronal nitric oxide synthase in the release of 6-nitrodopamine from mouse isolated vas deferens

Autor(es)

Britto-Junior, Jose ; Silva, Samuel Goulart Nacario ; Lima, Antonio Tiago ; Fuguhara, Vivian ; Andrade, Larissa Bueno ; Mendes, Gustavo Duarte ; Peterson, Larryn W. ; Chiavegatto, Silvana ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 143, p. 8-pg., 2023-12-16.

Resumo

6-Nitrodopamine (6-ND) is released from rat and human vas deferens and is considered a major mediator of both tissues contractility. The contractions induced by 6-ND are selectively blocked by both tricyclic antidepressants and alpha 1-adrenoceptor antagonists. Endothelial nitric oxide synthase (eNOS) is the major isoform responsible for 6ND release in mouse isolated heart, however the origin of 6-ND in the vas deferens is unknown. Here it was investigated by LC-MS/MS the basal release of 6-ND from isolated vas deferens obtained from control, eNOS-/-, nNOS-/-, and iNOS- /- mice. In addition, it was evaluated in vitro vas deferens contractility following electric field stimulation (EFS).Basal release of 6-ND was significantly reduced in nNOS-/- mice compared to control mice, but not decreased when the vas deferens were obtained from either eNOS-/- or iNOS-/- mice. Pre-incubation of the vas deferens with tetrodotoxin (1 mu M) significantly reduced the basal release of 6-ND from control, eNOS- /-, and iNOS-/mice but had no effect on the basal release of 6-ND from nNOS-/- mice. EFS-induced frequency-dependent contractions of the vas deferens, which were significantly reduced when the tissues obtained from control, eNOS-/- and iNOS- /- mice, were pre-incubated with L-NAME, but unaltered when the vas deferens was obtained from nNOS-/- mice. In addition, the EFS-induced contractions were significantly smaller when the vas deferens were obtained from nNOS-/- mice.The results clearly demonstrate that nNOS is the main NO isoform responsible for 6-ND release in mouse vas deferens and reinforces the concept of 6-ND as a major modulator of vas deferens contractility. (AU)

• Processo FAPESP: 17/06100-8 - Suscetibilidade e resiliência aos efeitos do estresse psicossocial crônico na adolescência: estudo da participação da enzima neuronal de síntese do óxido nítrico (nNOS)
• Beneficiário: Silvana Chiavegatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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: 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
• Processo FAPESP: 23/03503-5 - Avaliação da ação de 6-nitrodopamina no sistema cardiovascular em camundongos nocautes eNOS, nNOS e iNOS
• Beneficiário: Larissa Bueno Andrade
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica