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

2023; Elsevier BV; Volume: 143; Linguagem: Inglês

10.1016/j.niox.2023.12.002

1089-8611

José Britto‐Júnior, Samuel Goulart Nacário Silva, Antonio Tiago Lima, Vivian Fuguhara, Larissa Bueno Andrade, Gustavo Duarte Mendes, Larryn W. Peterson, Silvana Chiavegatto, Edson Antunes, Gilberto De Nucci,

Ion channel regulation and function

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 α1-adrenoceptor antagonists. Endothelial nitric oxide synthase (eNOS) is the major isoform responsible for 6-ND 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 μM) 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.