title: Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension.
  
  
  METHODS
  Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin.
  
  
  RESULTS
  ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females.
  
  
  CONCLUSIONS
  The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Dai
authors.affiliation: Department of Pathology, Hebei North University, Zhangjiakou, China.
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: J-J
authors.initials: JJ
authors.lastname: He
authors.affiliation: Life Science Research Center and Department of Physiology and Pathophysiology, Hebei North University, Zhangjiakou, China.
authors.forename: W
authors.initials: W
authors.lastname: Peng
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics; D013356:Subfornical Organ / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000633:toxicity
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II
keywords: angiotensin II; blood pressure; endoplasmic reticulum stress; sex difference; subfornical organ