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Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension.
Am J Physiol Heart Circ Physiol 2017; 313(6):H1075-H1086AJ

Abstract

The orexin system is involved in arginine vasopressin (AVP) regulation, and its overactivation has been implicated in hypertension. However, its role in salt-sensitive hypertension (SSHTN) is unknown. Here, we tested the hypothesis that hyperactivity of the orexin system in the paraventricular nucleus (PVN) contributes to SSHTN via enhancing AVP signaling. Eight-week-old male Dahl salt-sensitive (Dahl S) and age- and sex-matched Sprague-Dawley (SD) rats were placed on a high-salt (HS; 8% NaCl) or normal-salt (NS; 0.4% NaCl) diet for 4 wk. HS intake did not alter mean arterial pressure (MAP), PVN mRNA levels of orexin receptor 1 (OX1R), or OX2R but slightly increased PVN AVP mRNA expression in SD rats. HS diet induced significant increases in MAP and PVN mRNA levels of OX1R, OX2R, and AVP in Dahl S rats. Intracerebroventricular infusion of orexin A (0.2 nmol) dramatically increased AVP mRNA levels and immunoreactivity in the PVN of SD rats. Incubation of cultured hypothalamus neurons from newborn SD rats with orexin A increased AVP mRNA expression, which was attenuated by OX1R blockade. In addition, increased cerebrospinal fluid Na+ concentration through intracerebroventricular infusion of NaCl solution (4 µmol) increased PVN OX1R and AVP mRNA levels and immunoreactivity in SD rats. Furthermore, bilateral PVN microinjection of the OX1R antagonist SB-408124 resulted in a greater reduction in MAP in HS intake (-16 ± 5 mmHg) compared with NS-fed (-4 ± 4 mmHg) anesthetized Dahl S rats. These results suggest that elevated PVN OX1R activation may contribute to SSHTN by enhancing AVP signaling.NEW & NOTEWORTHY To our best knowledge, this study is the first to investigate the involvement of the orexin system in salt-sensitive hypertension. Our results suggest that the orexin system may contribute to the Dahl model of salt-sensitive hypertension by enhancing vasopressin signaling in the hypothalamic paraventricular nucleus.

Authors+Show Affiliations

Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan. Institute for Nursing and Health Research, Henan University, Kaifeng, China.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan.Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia; and.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan. Biotech Research Center, Michigan Technological University, Houghton, Michigan.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; zhiyings@mtu.edu. Biotech Research Center, Michigan Technological University, Houghton, Michigan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28667055

Citation

Huber, Michael J., et al. "Increased Activity of the Orexin System in the Paraventricular Nucleus Contributes to Salt-sensitive Hypertension." American Journal of Physiology. Heart and Circulatory Physiology, vol. 313, no. 6, 2017, pp. H1075-H1086.
Huber MJ, Fan Y, Jiang E, et al. Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension. Am J Physiol Heart Circ Physiol. 2017;313(6):H1075-H1086.
Huber, M. J., Fan, Y., Jiang, E., Zhu, F., Larson, R. A., Yan, J., ... Shan, Z. (2017). Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension. American Journal of Physiology. Heart and Circulatory Physiology, 313(6), pp. H1075-H1086. doi:10.1152/ajpheart.00822.2016.
Huber MJ, et al. Increased Activity of the Orexin System in the Paraventricular Nucleus Contributes to Salt-sensitive Hypertension. Am J Physiol Heart Circ Physiol. 2017 Dec 1;313(6):H1075-H1086. PubMed PMID: 28667055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension. AU - Huber,Michael J, AU - Fan,Yuanyuan, AU - Jiang,Enshe, AU - Zhu,Fengli, AU - Larson,Robert A, AU - Yan,Jianqun, AU - Li,Ningjun, AU - Chen,Qing-Hui, AU - Shan,Zhiying, Y1 - 2017/06/30/ PY - 2016/12/13/received PY - 2017/05/08/revised PY - 2017/06/22/accepted PY - 2017/7/2/pubmed PY - 2017/12/13/medline PY - 2017/7/2/entrez KW - orexin KW - paraventricular nucleus KW - salt-sensitive hypertension KW - sympathetic nerve activity KW - vasopressin SP - H1075 EP - H1086 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 313 IS - 6 N2 - The orexin system is involved in arginine vasopressin (AVP) regulation, and its overactivation has been implicated in hypertension. However, its role in salt-sensitive hypertension (SSHTN) is unknown. Here, we tested the hypothesis that hyperactivity of the orexin system in the paraventricular nucleus (PVN) contributes to SSHTN via enhancing AVP signaling. Eight-week-old male Dahl salt-sensitive (Dahl S) and age- and sex-matched Sprague-Dawley (SD) rats were placed on a high-salt (HS; 8% NaCl) or normal-salt (NS; 0.4% NaCl) diet for 4 wk. HS intake did not alter mean arterial pressure (MAP), PVN mRNA levels of orexin receptor 1 (OX1R), or OX2R but slightly increased PVN AVP mRNA expression in SD rats. HS diet induced significant increases in MAP and PVN mRNA levels of OX1R, OX2R, and AVP in Dahl S rats. Intracerebroventricular infusion of orexin A (0.2 nmol) dramatically increased AVP mRNA levels and immunoreactivity in the PVN of SD rats. Incubation of cultured hypothalamus neurons from newborn SD rats with orexin A increased AVP mRNA expression, which was attenuated by OX1R blockade. In addition, increased cerebrospinal fluid Na+ concentration through intracerebroventricular infusion of NaCl solution (4 µmol) increased PVN OX1R and AVP mRNA levels and immunoreactivity in SD rats. Furthermore, bilateral PVN microinjection of the OX1R antagonist SB-408124 resulted in a greater reduction in MAP in HS intake (-16 ± 5 mmHg) compared with NS-fed (-4 ± 4 mmHg) anesthetized Dahl S rats. These results suggest that elevated PVN OX1R activation may contribute to SSHTN by enhancing AVP signaling.NEW & NOTEWORTHY To our best knowledge, this study is the first to investigate the involvement of the orexin system in salt-sensitive hypertension. Our results suggest that the orexin system may contribute to the Dahl model of salt-sensitive hypertension by enhancing vasopressin signaling in the hypothalamic paraventricular nucleus. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/28667055/Increased_activity_of_the_orexin_system_in_the_paraventricular_nucleus_contributes_to_salt_sensitive_hypertension_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.00822.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -