title: Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension.
abstract: This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1-7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1-7), an ANG-(1-7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1-7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1-7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1-7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS.
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, Iowa; baojian-xue@uiowa.edu.
authors.forename: Baojian
authors.initials: B
authors.lastname: Xue
authors.affiliation: Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Henan, China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, Iowa;
authors.forename: Terry G
authors.initials: TG
authors.lastname: Beltz
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, Iowa;
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Physiology, University of Arizona, Tucson, Arizona; Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona; and.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hay
authors.affiliation: Department of Psychology, University of Iowa, Iowa City, Iowa; Department of Pharmacology, University of Iowa, Iowa City, Iowa; Francois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, Iowa;
authors.forename: Alan Kim
authors.initials: AK
authors.lastname: Johnson
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D005260:Female; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D057967:Infusions, Intraventricular; D008297:Male; D010052:Ovariectomy; D010446:Peptide Fragments / Q000008:administration & dosage; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D012737:Sex Factors; D013686:Telemetry; D013997:Time Factors
chemical_list: C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D004958:Estradiol; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: angiotensin II; angiotensin-(1–7), central nervous system; blood pressure; sex difference