| Full text | |
| Author(s): |
Magalhaes, Karolyne S.
;
Martins Sa, Renato W.
;
Salim, Nathalia
;
da Silva, Thais Marques
;
Machado, Benedito H.
;
Paton, Julian F. R.
;
Moraes, Davi J. A.
Total Authors: 7
|
| Document type: | Journal article |
| Source: | Circulation Research; v. 138, n. 2, p. 18-pg., 2026-01-16. |
| Abstract | |
BACKGROUND:Hypertension is the single most important risk factor for cardiovascular diseases and remains poorly controlled. Currently, 40% of treated patients remain hypertensive. We propose that this is in part due to excessive sympathetic activity. We hypothesized that neuronal expiratory oscillations, in the medullary lateral parafacial (pFL) region, become activated in conditions of neurogenic hypertension and that silencing their activity would be antihypertensive.METHODS:pFL neurons were manipulated by viral transfection. Using optogenetic and pharmacogenetic modulation, pFL neurons were either excited or inhibited in rats while recording sympathetic neurons from the rostral ventrolateral medulla (RVLM) and pontine noradrenergic A5 region, sympathetic activity, respiratory motor outflows, and arterial pressure from normotensive and hypertensive rats in vitro, in situ, and in vivo. Rats were made neurogenically hypertensive using chronic intermittent hypoxia.RESULTS:Optogenetic activation of pFL neurons triggered active expiration and positively modulated sympathetic activity during expiration, causing blood pressure to rise. pFL neurons projected to the RVLM and A5 presympathetic neurons and excited them during expiration, but in hypertension, only the pFL-RVLM synaptic transmission was enhanced. Pharmacogenetic inhibition of pFL neurons eliminated the expiratory-related sympatho-excitation and normalized arterial pressure in hypertensive rats.CONCLUSIONS:The heightened sympathetic activity inducing hypertension triggered by chronic intermittent hypoxia is caused, in the most part, by the emergence of pFL expiratory oscillations driving RVLM and A5 sympathetic vasomotor neurons and active expiration simultaneously. We propose that suppressing pFL neurons would have therapeutic potential. (AU) | |
| FAPESP's process: | 18/15957-2 - Astrocytic modulation on brainstem neurons involved with generation and control of sympathetic and respiratory activities in rodents submitted to hypoxia |
| Grantee: | Benedito Honorio Machado |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 23/02560-5 - Involvement of the somatostatinergic interneurons of the lateral parafacial region in the generation of active expiration in mice |
| Grantee: | Nathalia Salim |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 22/02138-9 - The role of astrocytes of the lateral parafacial region in the central generation of expiratory and sympathetic activities and in the control of cardiovascular function in mice. |
| Grantee: | Renato Willian Martins Sá |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 22/07579-3 - Experimental periodontitis in genetically modified mice (VAChT and Super VAChT): cardiovascular and inflammatory aspects |
| Grantee: | Thaís Marques da Silva |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/24060-9 - Contribution of the parafacial Respiratory Group to the inspiratory, expiratory and cardiovascular responses of rats to muscle afferent fiber stimulation |
| Grantee: | Karolyne Silva Magalhães |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| 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 |