Telmisartan Ameliorates Blood-Brain Barrier Disruption in a High-Salt Diet Mouse Model

The disruption of the blood-brain barrier (BBB) in hypertension is a critical pathophysiological event characterized by an increase in barrier permeability, which can potentially lead to severe neurological complications. Telmisartan, an angiotensin II receptor antagonist (ARB), is widely prescribed for the management of hypertension. However, there is limited literature on the specific effects of Telmisartan on BBB disruption associated with high-salt diet (HSD)-induced changes. In this study, a salt-induced hypertensive state was induced in mice using a HSD to investigate the effects of telmisartan on BBB disruption associated with HSD. Our recent findings indicate that Telmisartan mitigates brain vascular endothelial inflammation and reduces BBB permeability in HSD-treated mice. Specifically, it downregulates the messenger RNA (mRNA) and protein expression levels of intercellular adhesion molecule-1 (ICAM-1) and endothelial selectin (E-selectin). Additionally, Telmisartan inhibits BBB permeability as evidenced by reduced extravasation of Evans blue dye and restores the expression of Claudin-1, a crucial tight junction (TJ) protein. In vitro studies further support these findings, demonstrating that Telmisartan effectively reduces Angiotensin II-induced permeability in human brain microvascular endothelial cells (HBMECs). Moreover, Telmisartan treatment leads to an increase in trans-endothelial electrical resistance (TEER), indicative of improved barrier function. It also restores the expression of Claudin-1, prevents endothelial dysfunction, and activates the Wnt/β-catenin signaling pathway. Notably, silencing the β-catenin pathway abrogates the beneficial effects of Telmisartan, suggesting that the protective actions of Telmisartan on BBB integrity in HSD-induced conditions are mediated through the activation of the Wnt/β-catenin signaling pathway. These results collectively suggest that Telmisartan not only effectively manages HSD-induced hypertension but also exerts neuroprotective effects by preserving BBB integrity. This dual functionality positions Telmisartan as a potentially valuable therapeutic agent for patients at risk for neurological complications due to HSD-induced BBB disruption.