| Texto completo | |
| Autor(es): |
Raquel, Hiviny de Ataides
;
Makuch-Martins, Mariana
;
Perego, Sany M.
;
Masson, Gustavo S.
;
Jensen, Leonardo
;
Michelini, Lisete C.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Clinical Science; v. 139, n. 11, p. 17-pg., 2025-05-01. |
| Resumo | |
Reduced ventricular function, renin-angiotensin system up-regulation, and sympathoexcitation are hallmarks of heart failure (HF). Recently, we showed that blood-brain barrier (BBB) lesion within autonomic nuclei contributes to autonomic imbalance and that exercise training (T) normalizes BBB function and improves autonomic control. We sought now to identify the mechanism(s) involved in both HF-induced lesion and exercise-induced correction. Wistar rats submitted to coronary artery ligation were, after the development of HF, assigned to losartan (Los) or vehicle (Veh) treatments and simultaneously submitted to T or sedentary (S) protocol. After hemodynamic/autonomic recordings and evaluation of BBB permeabil- ity, brains were harvested for ultrastructural analyses of the barrier (tight junctions' [TJs] tightness and vesicles trafficking) within capillaries of the hypothalamic paraventricular nucleus. Local angiotensin II (Ang II) expression and activation of microglial cells (IBA-1 immunofluorescence) were also evaluated. High sympathetic activity and pressure variability, reduced parasympathetic control of the heart, elevated BBB permeability, high vesicular trafficking, and TJ weakness exhibited by Veh-S rats were equally corrected in Veh-T, Los-S, and Los-T groups. The increased paraventricular hypothalamic nucleus (PVN) Ang II expression and IBA-1 density in Veh-S group were similarly reduced by T, Los and combination of both. Ang II, colocalized with microglia AT1 receptors, induced their remodeling from disease-associated phenotype in Veh-S rats to homeostatic-surveilling conditions in the other groups. All measured parameters exhibited strong correlations with Ang II availability. Data indicated that changes in PVN Ang II availability induced by HF, exercise, and Los are the key regulator of transcellular and paracellular transport across the BBB. (AU) | |
| Processo FAPESP: | 18/14544-6 - Barreira hematoencefálica: um novo paradigma no tratamento da hipertensão |
| Beneficiário: | Lisete Compagno Michelini |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/22156-3 - Efeitos da insuficiência cardíaca e do treinamento aeróbio sobre a integridade da barreira hematoencefálica em áreas de controle autonômico: Mecanismos envolvidos no transporte paracelular e transcelular. |
| Beneficiário: | Hiviny de Ataides Raquel |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |