title: Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation.
abstract: This study aims to understand the special expression patterns of angiotensin-II receptor (AT1R and AT2R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT1R and AT2R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT2R expression were also tested. The data showed that AT2R, rather than AT1R, expression was higher in female than age-matched male rats. Moreover, AT2R was downregulated in ovariectomized rats, which was restored by the administration of 17β-estradiol. Single-cell real time-polymerase chain reaction data indicated that AT2R was uniquely expressed in Ah-type BRNs. Functional study showed that long-term administration of 17β-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah- than C-type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed by iberiotoxin. The density of angiotensin-II-sensitive K(+) currents recorded in Ah-types was equivalent with iberiotoxin-sensitive component. In summary, the unique, sex- and afferent-specific expression of AT2R was identified in Ah-type BRNs, and AT2R-mediated KCa1.1 inhibition in Ah-type BRNs may exert great impacts on baroreflex afferent function and blood pressure regulation in females.
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: He
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Han
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Liang
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Lu-Qi
authors.initials: LQ
authors.lastname: Wang
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Lu
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.).
authors.forename: Hanying
authors.initials: H
authors.lastname: Chen
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.). liby@ems.hrbmu.edu.cn qiaogf88@163.com wshou@iu.edu.
authors.forename: Guo-Fen
authors.initials: GF
authors.lastname: Qiao
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.). liby@ems.hrbmu.edu.cn qiaogf88@163.com wshou@iu.edu.
authors.forename: Weinian
authors.initials: W
authors.lastname: Shou
authors.affiliation: From the Department of Pharmacology (Y.L., J.-Y.Z., Y.-H.Z., D.W., J.-L.H., L.-M.H., X.-B.L., L.-Q.W., X.-L.L., G.-F.Q., B.-Y.L.) and Key Laboratory of Cardiovascular Medicine Research of Ministry of Education (Y.-H.Z., D.W., L.-Q.W., X,-B.L., G.-F.Q.), Harbin Medical University, Harbin, Heilongjiang, China; Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis (H.C., W.S.). liby@ems.hrbmu.edu.cn qiaogf88@163.com wshou@iu.edu.
authors.forename: Bai-Yan
authors.initials: BY
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000378:metabolism; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009620:Nodose Ganglion / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II
keywords: action potentials; angiotensin II receptor; baroreflex; blood pressure; ion channels