Pretreatment with NaHS attenuated Ang II-induced spatial learning deficits and synaptic protein perturbation by suppressing neuroinflammation and endothelial NOX2 expression.
Does NaHS (H2S donor) improve spatial learning and reduce neuroinflammation in rats with Angiotensin II-induced hypertension?
Hydrogen sulfide supplementation mitigates hypertension-induced spatial learning deficits by suppressing neuroinflammation and endothelial NOX2 expression in a rat model.
Abstract Hypertension (HTN), when prolonged, extends beyond the cardiovascular system, impairs neurovascular function, and progresses into cognitive impairment. Thus, it is essential to understand the mechanism that drives HTN-induced brain pathogenesis for devising novel therapy. This study explored spatial learning, vessels-associated microglia and neuroinflammation during angiotensin II (Ang II) induced HTN with the hypothesis that after HTN induction, endogenous H 2 S level contributes to neuropathology in HTN. Male Sprague Dawley rats received Ang II (600 ng/kg/min) or saline using an implanted osmotic pump, and NaHS (4 mg/kg), an H 2 S donor was given intraperitoneally 10 days prior and during Ang II infusion. We employed H 2 S estimation by amperometric probe, spatial learning was assessed through the Morris water maze task, and synaptic proteins were probed in a synaptosomal fraction of hippocampus homogenate using Western blot. Additionally, rat cytokine array and immunofluorescence were used to screen for chemokine and cytokine, and the endothelium microglial phenotype, respectively. The pretreatment of NaHS attenuated Ang II-induced spatial learning and perturbation of synaptic protein in the hippocampus. It is associated with significant reduction in endothelial activation and microglia pro-inflammatory phenotype in both parenchymal and vessel-associated microglia. Moreover, above observation is accompanied by decreased proinflammatory cytokines and chemokines, such as, TNF-α, MCP-1, VEGF, and IL-1ɑ, among others. In summary, our data demonstrated that maintenance of H 2 S level attenuated HTN induced spatial learning deficit by suppressing neuroinflammation and endothelial NOX2 expression. Therefore, reinforcing the role of H 2 S in alleviating oxidant-induced inflammatory injury and eventually maintaining brain function.
Kumar et al. (Sat,) conducted a other in Angiotensin II-induced hypertension. NaHS (H2S donor) vs. Saline was evaluated on Spatial learning and neuroinflammation. Pretreatment with NaHS attenuated Ang II-induced spatial learning deficits and synaptic protein perturbation by suppressing neuroinflammation and endothelial NOX2 expression.