| Full text | |
| Author(s): Show less - |
Lataro, Renata M.
;
Moraes, Davi J. A.
;
Gava, Fabio N.
;
Omoto, Ana C. M.
;
Silva, Carlos A. A.
;
Brognara, Fernanda
;
Alflen, Lais
;
Brazao, Vania
;
Colato, Rafaela Pravato
;
do Prado, Jose' Clo'vis
;
Ford, Anthony P.
;
Salgado, Helio C.
;
Paton, Julian F. R.
Total Authors: 13
|
| Document type: | Journal article |
| Source: | NATURE COMMUNICATIONS; v. 14, n. 1, p. 14-pg., 2023-03-28. |
| Abstract | |
Despite advances in the treatment of heart failure, prognosis is poor, mortality high and there remains no cure. Heart failure is associated with reduced cardiac pump function, autonomic dysregulation, systemic inflammation and sleep-disordered breathing; these morbidities are exacerbated by peripheral chemoreceptor dysfunction. We reveal that in heart failure the carotid body generates spontaneous, episodic burst discharges coincident with the onset of disordered breathing in male rats. Purinergic (P2X3) receptors were upregulated two-fold in peripheral chemosensory afferents in heart failure, and when antagonized abolished these episodic discharges, normalized both peripheral chemoreceptor sensitivity and the breathing pattern, reinstated autonomic balance, improved cardiac function, and reduced both inflammation and biomarkers of cardiac failure. Aberrant ATP transmission in the carotid body triggers episodic discharges that via P2X3 receptors play a crucial role in the progression of heart failure and as such offer a distinct therapeutic angle to reverse multiple components of its pathogenesis. Despite medications, heart failure worsens with time with many patients dying within five years of diagnosis. Here the authors show that blocking purinergic receptors in the carotid body stops heart failure progression, improves its function, reduces sleep apneas and systemic inflammation in male rats. (AU) | |
| FAPESP's process: | 21/06886-7 - Role of purinergic receptors in the carotid body in heart failure |
| Grantee: | Davi José de Almeida Moraes |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 13/20549-7 - New insights in cardiovascular regulation under physiological and pathophysiological condition |
| Grantee: | Helio Cesar Salgado |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/11863-6 - Synaptic transmission and electrophysiological properties of bronchial motoneurons of the dorsal motor nucleus of the vagus from rats |
| Grantee: | Davi José de Almeida Moraes |
| Support Opportunities: | Regular Research Grants |