Date of Award

2026

Document Type

Open Access Master's Thesis

Degree Name

Master of Science in Biological Sciences (MS)

Administrative Home Department

Department of Biological Sciences

Advisor 1

Zhiying Shan

Committee Member 1

Qing-Hui Chen

Committee Member 2

Lanrong Bi

Committee Member 3

Robert Larson

Abstract

Hypertension remains a leading risk factor for cardiovascular disease with incompletely understood central mechanisms. Orexinergic signaling in the paraventricular nucleus (PVN) has been linked to neurogenic hypertension, but the mechanisms remain unclear. Astrocytes have emerged as active participants in autonomic regulation, but their role in orexinergic signaling in the PVN remains unknown. We tested whether PVN orexin receptor 1 (OX1R) regulates astrocytic aquaporin-4 (AQP4) in orexin-driven sympathoexcitation and blood pressure elevation. Rats with PVN AAV2-OX1R transfection showed chronically elevated blood pressure and selective PVN astrocytic AQP4 upregulation (1.9-fold, P,0.05). In cultured astrocytes, OX1R knockdown and overexpression produced parallel changes in AQP4, whereas acute orexin A treatment increased AQP4 protein only in control cells. PVN microinjection of the AQP4 blocker TGN-020 alone produced pressor and sympathoexcitatory responses and enhanced the sympathetic response to orexin A (P< 0.05), an effect absent in PVN OX1R-overexpressing rats. Renal AQP2 and AQP4 immunoreactivity decreased in PVN OX1R-overexpressing rats, arguing against peripheral vasopressin-driven fluid retention. These findings identify PVN OX1R regulation of astrocytic AQP4 as a novel mechanism potentially underlying neurogenic hypertension.

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