title: Activation of microglia within paraventricular nucleus of hypothalamus is NOT involved in maintenance of established hypertension.
abstract: Inflammation within paraventricular nucleus of the hypothalamus (PVN), a key circulatory control center in the hypothalamus, is an important pathology of sympathetic hyperactivity. Brain inflammation is mainly mediated by microglia, innate immune cells in the brain. Activated microglia produce inflammatory cytokines with alteration of their morphology. Increase in inflammatory cytokines synthesis coincides with activation of microglia within PVN of angiotensin II-induced hypertensive model and myocardial infarction-induced heart failure model. Although the increase in inflammatory cytokines and the microglial activation within PVN were also seen in spontaneously hypertensive rats (SHR), the model of essential hypertension, their involvement in blood pressure regulation has still be fully clarified. In the present study, we examined whether activated microglia within PVN were involved in maintenance of established severe hypertension with sympathoexcitation.
  
  
  
  Minocycline (25mg/kg/day), an inhibitor of microglial activation, or vehicle were orally administered to stroke-prone SHR (SHRSP) and normotensive Wistar-Kyoto (WKY) rats for 2 weeks from 15-weeks-old, the age of established hypertension.
  
  
  
  Systolic blood pressure was comparable between minocycline treated-SHRSP and vehicle treated-SHRSP, whereas morphological analysis of microglia revealed smaller cell size in minocycline treated-SHRSP than vehicle treated-SHRSP, implying that minocycline deactivated microglia within PVN.
  
  
  
  Activated microglia with morphological alteration within PVN are not involved in the maintenance of established severe hypertension, and inflammation within PVN could not be the therapeutic target of established hypertension.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Takesue
authors.affiliation: Department of Collaborative Research Institute of Innovation for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan. Electronic address: tkishi@cardiol.med.kyushu-u.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Advanced Cardiovascular Regulation and Therapeutics for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.affiliation: Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D017628:Microglia / Q000502:physiology*; D008911:Minocycline / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline
keywords: Brain; Glia; Hypertension; Inflammation