title: Central Infusion of Angiotensin II Type 2 Receptor Agonist Compound 21 Attenuates DOCA/NaCl-Induced Hypertension in Female Rats.
abstract: The present study investigated whether central activation of angiotensin II type 2 receptor (AT2-R) attenuates deoxycorticosterone acetate (DOCA)/NaCl-induced hypertension in intact and ovariectomized (OVX) female rats and whether female sex hormone status has influence on the effects of AT2-R activation. DOCA/NaCl elicited a greater increase in blood pressure in OVX females than that in intact females. Central infusion of compound 21, a specific AT2-R agonist, abolished DOCA/NaCl pressor effect in intact females, whereas same treatment in OVX females produced an inhibitory effect. Real-time RT-PCR analysis revealed that DOCA/NaCl enhanced the mRNA expression of hypertensive components including AT1-R, ACE-1, and TNF-α in the paraventricular nucleus of hypothalamus in both intact and OVX females. However, the mRNA expressions of antihypertensive components such as AT2-R, ACE-2, and IL-10 were increased only in intact females. Central AT2-R agonist reversed the changes in the hypertensive components in all females, while this agonist further upregulated the expression of ACE2 and IL-10 in intact females, but only IL-10 in OVX females. These results indicate that brain AT2-R activation plays an inhibitory role in the development of DOCA/NaCl-induced hypertension in females. This beneficial effect of AT2-R activation involves regulation of renin-angiotensin system and proinflammatory cytokines.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Dai
authors.affiliation: Department of Pathophysiology, Hebei North University, Zhangjiakou, Hebei 075000, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Life Science Research Center, Hebei North University, Zhangjiakou, Hebei 075000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: He
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D064791:Desoxycorticosterone Acetate; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D057967:Infusions, Intraventricular; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; C494557:N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; D013876:Thiophenes; D064791:Desoxycorticosterone Acetate