Chronic Paraventricular OX1R Overexpression Induces Oxidative Stress and Hypertension in Rats
Document Type
Article
Publication Date
2-11-2026
Department
Department of Kinesiology and Integrative Physiology; Department of Biological Sciences; Department of Chemistry; Health Research Institute
Abstract
Background Hyperactivity of the orexin system has been implicated in hypertension, yet the long-term impact of orexin 1 receptor (OX1R) overexpression in the paraventricular nucleus (PVN), a key brain region involved in arterial blood pressure (ABP) regulation, remains unclear. This study examined whether chronic OX1R overexpression in the PVN alters cardiovascular, neuroendocrine, and oxidative functions.
Methods Adult male Sprague–Dawley rats received bilateral PVN injections of AAV2-OX1R or control virus AAV2-GFP. Their ABP and heart rate (HR) were monitored for eight weeks via radiotelemetry. Renal sympathetic nerve activity (RSNA) and ABP responses to PVN orexin A administration were assessed using in vivo recordings. Reactive oxygen species (ROS) were quantified using MitoProbe, and gene expression was analyzed by qPCR. Primary neuronal cultures were used to explore underlying mechanism involved in increased ROS production and neuronal activity.
Results PVN OX1R overexpression increased mean ABP (∼10 mmHg), water intake, and ROS levels in both the PVN and peripheral organs. In addition, orexin A evoked exaggerated RSNA (155% vs. 73%) and pressor responses (27 vs. 16 mmHg) in PVN OX1R overexpression rats compared to control rats, these effects were attenuated by the OX1R antagonist SB408124. Plasma vasopressin levels were elevated, and brain sections confirmed increased ROS in OX1R-positive neurons. In vitro experiments further demonstrated that orexin A upregulated ROS-generating enzymes, suppressed antioxidant genes, and enhanced neuronal excitability.
Conclusion Chronic PVN OX1R overexpression induces oxidative stress, sympathetic overactivity, and increased plasma vasopressin, contributing to hypertension development. Targeting PVN OX1R signaling may provide therapeutic benefit for hypertension.
Publication Title
bioRxiv : the preprint server for biology
Recommended Citation
Huang, P.,
Yousefzadehkharvanagh, N.,
Simet, D.,
Chen, X.,
Li, Y.,
Larson, R.,
Bi, L.,
Chen, Q.,
Chen, B.,
&
Shan, Z.
(2026).
Chronic Paraventricular OX1R Overexpression Induces Oxidative Stress and Hypertension in Rats.
bioRxiv : the preprint server for biology.
http://doi.org/10.64898/2026.02.09.704927
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p2/2687
Version
Preprint