title: Microglia participate in neurogenic regulation of hypertension.
abstract: Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure.
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Shen
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Kandarp H
authors.initials: KH
authors.lastname: Shah
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Bernstein
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lyden
authors.affiliation: From the Departments of Biomedical Sciences (X.Z.S., K.H.S., K.E.B.), Neurology (Y.L., L.L., P.L., P.S.), and Pathology and Laboratory Medicine (X.Z.S., K.E.B.), Cedars-Sinai Medical Center, Los Angeles, CA. Peng.Shi@cshs.org.
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000502:physiology*; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D057967:Infusions, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D004167:Diphtheria Toxin; D000804:Angiotensin II; D019331:NG-Nitroarginine Methyl Ester
keywords: angiotensin; hypertension; microglia; neuroimmunomodulation