| Title: |
Increased absorptive transcytosis and tight junction weakness in heart failure are equally corrected by exercise training and losartan |
| Authors: |
de Ataides Raquel, Hiviny; Makuch-Martins, Mariana; Perego, Sany M.; Masson, Gustavo S.; Jensen, Leonardo; Michelini, Lisete C. |
| Contributors: |
Fundação de Amparo à Pesquisa do Estado de São Paulo; Conselho Nacional de Desenvolvimento Científico e Tecnológico |
| Source: |
Clinical Science ; volume 139, issue 11, page 527-543 ; ISSN 0143-5221 1470-8736 |
| Publisher Information: |
Portland Press Ltd. |
| Publication Year: |
2025 |
| Description: |
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 permeability, 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1042/cs20242965 |
| Availability: |
https://doi.org/10.1042/cs20242965; https://portlandpress.com/clinsci/article-pdf/139/11/527/973090/cs-2024-2965.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.FF216DC7 |
| Database: |
BASE |