ArticleAmerican journal of physiology. Heart and circulatory physiology2016
Cross talk between AT1 receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 114 citations in OpenAlex.
- Role of Exercise in Modulating the Brain-Heart Axis in Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- Ang II-mediated effects on BBB integrity in psychiatric and neurological disorders.Progress in neuro-psychopharmacology & biological psychiatry · 2026Review
- The brain-heart axis: effects of cardiovascular disease on the CNS and opportunities for central neuromodulation.Nature reviews. Neuroscience · 2026Review
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- The application of telmisartan in central nervous system disorders.Pharmacological reports : PR · 2025Review
- Chronic Copper Overload Triggers Inflammation in Mesenteric PVAT Alongside Changes in Renin-Angiotensin System-Related Pathways.Nutrients · 2025Article
- Obesity- and High-Fat-Diet-Induced Neuroinflammation: Implications for Autonomic Nervous System Dysfunction and Endothelial Disorders.International journal of molecular sciences · 2025Review
- Development of cerebral microhemorrhages in a mouse model of hypertension.Journal of neuroinflammation · 2025Article
- Definitive Evidence for the Identification and Function of Renin-Expressing Cholinergic Neurons in the Nucleus Ambiguus.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Intersecting epidemics: immune dysregulation associated with HIV and tuberculosis syndemic contribute to increased risk of hypertensive disease in Sub-Saharan Africa.Frontiers in cardiovascular medicine · 2025Review
- Immune system activation and cognitive impairment in arterial hypertension.American journal of physiology. Cell physiology · 2024Review
- Angiotensin-II drives changes in microglia-vascular interactions in rats with heart failure.Communications biology · 2024Article
- Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.Pflugers Archiv : European journal of physiology · 2024Article
- Neuroimmunology of Cardiovascular Disease.Current hypertension reports · 2024Review
- Angiotensin II, blood-brain barrier permeability, and microglia interplay during the transition from pre-to hypertensive phase in spontaneously hypertensive rats.Frontiers in physiology · 2024Article
- Angiotensin II-Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats.Hypertension (Dallas, Tex. : 1979) · 2023Article
- The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.Biomolecules · 2023Review
- Pathogenesis of Chronic Kidney Disease Is Closely Bound up with Alzheimer's Disease, Especially via the Renin-Angiotensin System.Journal of clinical medicine · 2023Review
- Cardiomyocyte-specific deletion of TLR4 attenuates angiotensin II-induced hypertension and cardiac remodeling.Frontiers in cardiovascular medicine · 2023Article
- Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases.Biomolecules · 2022Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ANG II is thought to increase sympathetic outflow by increasing oxidative stress and promoting local inflammation in the paraventricular nucleus (PVN) of the hypothalamus. However, the relative contributions of inflammation and oxidative stress to sympathetic drive remain poorly understood, and the underlying cellular and molecular targets have yet to be examined. ANG II has been shown to enhance Toll-like receptor (TLR)4-mediated signaling on microglia. Thus, in the present study, we aimed to determine whether ANG II-mediated activation of microglial TLR4 signaling is a key molecular target initiating local oxidative stress in the PVN. We found TLR4 and ANG II type 1 (AT1) receptor mRNA expression in hypothalamic microglia, providing molecular evidence for the potential interaction between these two receptors. In hypothalamic slices, ANG II induced microglial activation within the PVN (∼65% increase, P < 0.001), an effect that was blunted in the absence of functional TLR4. ANG II increased ROS production, as indicated by dihydroethidium fluorescence, within the PVN of rats and mice (P < 0.0001 in both cases), effects that were also dependent on the presence of functional TLR4. The microglial inhibitor minocycline attenuated ANG II-mediated ROS production, yet ANG II effects persisted in PVN single-minded 1-AT1a knockout mice, supporting the contribution of a non-neuronal source (likely microglia) to ANG II-driven ROS production in the PVN. Taken together, these results support functional interactions between AT1 receptors and TLR4 in mediating ANG II-dependent microglial activation and oxidative stress within the PVN. More broadly, our results support a functional interaction between the central renin-angiotensin system and innate immunity in the regulation of neurohumoral outflows from the PVN.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.