Title
Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension
Document Type
Article
Publication Date
12-1-2017
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.
Publication Title
American Journal of Physiology - Heart and Circulatory Physiology
Recommended Citation
Huber, M. J.,
Fan, Y.,
Jiang, E.,
Zhu, F.,
Larson, R.,
Yan, J.,
Li, N.,
Chen, Q.,
&
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), H1075-H1086.
http://doi.org/10.1152/ajpheart.00822.2016
Retrieved from: https://digitalcommons.mtu.edu/kip-fp/71
Publisher's Statement
© 2017 American Physiological Society. Publisher's version of record: https://doi.org/10.1152/ajpheart.00822.2016