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

Author(s)

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

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 143, p. 8-pg., 2023-12-16.

Abstract

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)

• FAPESP's process: 17/06100-8 - Susceptibility and resilience to the effects of chronic psychosocial stress in adolescence: participation of the neuronal nitric oxide synthase (nNOS)
• Grantee: Silvana Chiavegatto
• Support Opportunities: Regular Research 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: 22/07737-8 - Evaluation of the cardiovascular effect of 6-nitrodopamine in isolated atrium and perfused rat heart
• Grantee: Vivian Fuguhara de Lima
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 23/03503-5 - Evaluation of the action of 6-nitrodopamine on the cardiovascular system in eNOS, nNOS and iNOS knockout mice
• Grantee: Larissa Bueno Andrade
• Support Opportunities: Scholarships in Brazil - Scientific Initiation