Feil Family Brain & Mind Research Institute

You are here

Alterations in the subcellular distribution of NADPH oxidase p47(phox) in hypothalamic paraventricular neurons following slow-pressor angiotensin II hypertension in female mice with accelerated ovarian failure.

TitleAlterations in the subcellular distribution of NADPH oxidase p47(phox) in hypothalamic paraventricular neurons following slow-pressor angiotensin II hypertension in female mice with accelerated ovarian failure.
Publication TypeJournal Article
Year of Publication2016
AuthorsVan Kempen TA, Narayan A, Waters EM, Marques-Lopes J, Iadecola C, Glass MJ, Pickel VM, Milner TA
JournalJ Comp Neurol
Volume524
Issue11
Pagination2251-65
Date Published2016 Aug 01
ISSN1096-9861
KeywordsAngiotensin II, Animals, Disease Models, Animal, Female, Hypertension, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Microscopy, Immunoelectron, NADPH Oxidases, Neurons, Paraventricular Hypothalamic Nucleus, Postmenopause, Sex Characteristics
Abstract

At younger ages, women have a lower risk for hypertension than men, but this sexual dimorphism declines with the onset of menopause. These differences are paralleled in rodents following "slow-pressor" angiotensin II (AngII) administration: young male and aged female mice, but not young females, develop hypertension. There is also an established sexual dimorphism both in the cardiovascular response to the neurohypophyseal hormone arginine vasopressin (AVP) and in the expression of oxidative stress. We examined the relationship between AngII-mediated hypertension and the cellular distribution of the superoxide generating NADPH oxidase (NOX) in AVP-expressing hypothalamic paraventricular nucleus (PVN) neurons in "menopausal" female mice. Dual-labeling immunoelectron microscopy was used to determine whether the subcellular distribution of the organizer/adapter NOX p47(phox) subunit is altered in PVN dendrites following AngII administered (14 days) during the "postmenopausal" stage of accelerated ovarian failure (AOF) in young female mice treated with 4-vinylcyclohexene diepoxide. Slow-pressor AngII elevated blood pressure in AOF females and induced a significant increase in near plasmalemmal p47(phox) and a decrease in cytoplasmic p47(phox) in PVN AVP dendrites. These changes are the opposite of those observed in AngII-induced hypertensive male mice (Coleman et al. [2013] J. Neurosci. 33:4308-4316) and may be ascribed in part to baseline differences between young females and males in the near plasmalemmal p47(phox) on AVP dendrites seen in the present study. These findings highlight fundamental differences in the neural substrates of oxidative stress in the PVN associated with AngII hypertension in postmenopausal females compared with males. J. Comp. Neurol. 524:2251-2265, 2016. © 2015 Wiley Periodicals, Inc.

DOI10.1002/cne.23944
Alternate JournalJ. Comp. Neurol.
PubMed ID26659944
PubMed Central IDPMC4892978
Grant ListT32 DA007274 / DA / NIDA NIH HHS / United States
R21 AG039850 / AG / NIA NIH HHS / United States
R01 NS073666 / NS / NINDS NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL098351 / HL / NHLBI NIH HHS / United States
T32 DK007313 / DK / NIDDK NIH HHS / United States
R37 NS089323 / NS / NINDS NIH HHS / United States
P01 HL096571 / HL / NHLBI NIH HHS / United States