Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension

Michael J. Huber, Yuanyuan Fan, Enshe Jiang, Fengli Zhu, Robert A. Larson, Jianqun Yan, Ningjun Li, Qing-Hui Chen, Zhiying Shan
2017 American Journal of Physiology. Heart and Circulatory Physiology  
Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension. Am 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
more » ... ht-week-old male Dahl salt-sensitive (Dahl S) and ageand sex-matched Sprague-Dawley (SD) rats were placed on a highsalt (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 ϩ concentration through intracerebroventricular infusion of NaCl solution (4 mol) 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 (Ϫ16 Ϯ 5 mmHg) compared with NS-fed (Ϫ4 Ϯ 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 saltsensitive 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. paraventricular nucleus; orexin; salt-sensitive hypertension; sympathetic nerve activity; vasopressin * M. J. Huber and Y. Fan contributed equally to this work.
doi:10.1152/ajpheart.00822.2016 pmid:28667055 fatcat:4kinpnwoozfllpkf4srgnq3vzm