title: Neuroinflammatory mechanisms of hypertension: potential therapeutic implications.
abstract: Inflammation of forebrain and hindbrain nuclei has recently been highlighted as an emerging factor in the pathogenesis of neurogenic hypertension. The aim of this review is to summarize the state of the art in this field and to discuss recently discovered pathophysiological mechanisms, opening new perspectives for therapeutic application.
  
  
  
  Microglia Toll-like receptor 4 causally links angiotensin II (AngII)-mediated microglia cell activation and oxidative stress within the hypothalamic paraventricular nucleus (PVN). Toll-like receptor 4 can also be activated by lipopolysaccharides. PVN infusion of nuclear factor κB inhibitor lowers the blood pressure and ameliorates cardiac hypertrophy. Ang-(1-7) exerts direct effects on microglia, causing a reduction in both baseline and prorenin-induced release of proinflammatory cytokines. A compromised blood-brain barrier (BBB) constitutes a complementary mechanism that exacerbates AngII-driven neurohumoral activation, contributing to the development of hypertension.
  
  
  
  PVN and BBB seem to be pivotal targets for therapeutic intervention in hypertension. Recent advances in imaging techniques enable visualization of the inflammatory state in microglia and BBB integrity in humans. AngII type I receptor blockers and AngII-converting enzyme inhibitors are the most likely candidates for controlled randomized trials in humans aimed at amelioration of brain inflammation in the forthcoming years.
authors.affiliation: aInstitute of Human Physiology, Medical University of Gdansk, GdanskbDepartment of Immunopathology of Infectious and Parasitic DiseasescDepartment of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Pawel J
authors.initials: PJ
authors.lastname: Winklewski
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D012083:Renin / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D051197:Toll-Like Receptor 4; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7)