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Hypothalamic Activated Microglia Augment Blood Pressure Elevation during Early Developing Phase of Hypertension in Stroke‐prone Spontaneously Hypertensive Rats
Author(s) -
Takesue Ko,
Kishi Takuya,
Hirooka Yoshitaka
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1235.2
Subject(s) - microglia , blood pressure , medicine , endocrinology , minocycline , spontaneously hypertensive rat , inflammation , chemistry , antibiotics , biochemistry
Background Inflammation within the paraventricular nucleus of the hypothalamus (PVN) mediated by microglia with microglial morphological change is an important pathology of sympathoexcitation. Although previous reports showed activation of microglia within the PVN of angiotensin II‐induced hypertensive or spontaneously hypertensive rats (SHR), we did not confirmed that deactivation of microglia within the PVN could decrease blood pressure in hypertensive rats. Our previous data indicated that PVN microglia were much more activated at earlier stage of hypertension in stroke‐prone SHR (SHRSP) compared to normotensive Wistar‐Kyoto (WKY) rats. Therefore, We examined whether deactivation of microglia within the PVN could attenuate blood pressure elevation during early developing phase of hypertension in genetically hypertensive rats. Methods and results Six week‐old SHRSP and age‐matched normotensive WKY were intracerebroventriculary (ICV) administered minocycline (5 μg/h), microglial deactivator, for 4 weeks. ICV infusion of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8–9, P<0.05) but not in WKY. 24‐h urinary norepinephrine excretion tended to be lowered by minocycline infusion in SHRSP. Activation of microglia within the PVN, identified by microglia specific ionized calcium‐binding adaptor molecule 1 (Iba‐1) immunoreactivity, was evaluated by the roundness and perimeter of microglia. Minocycline significantly decreased roundness and increased perimeter of microglia, indicating deactivation of microglia, within the PVN of SHRSP. Conclusion Hypothalamic activated microglia with morphological alteration accelerate blood pressure elevation probably by sympathoexcitation during early developing phase of hypertension in SHRSP. Support or Funding Information This study was supported by a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (24390198 to Dr. Hirooka and 22790709 to Dr. Kishi).