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

Author(s)

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

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 138, p. 8-pg., 2023-06-12.

Abstract

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)

• 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: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
• Grantee: Gilberto de Nucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system
• Grantee: José Britto Júnior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral