Chronic Paraventricular OX1R Overexpression Induces Oxidative Stress and Hypertension in Rats

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Endocrinology

Background:

• Orexin system hyperactivity is linked to hypertension.
• The specific long-term effects of orexin 1 receptor (OX1R) overexpression in the paraventricular nucleus (PVN) on cardiovascular regulation are not fully understood.

Purpose of the Study:

• To investigate the impact of chronic OX1R overexpression in the PVN on cardiovascular, neuroendocrine, and oxidative functions.

Main Methods:

• Rats received viral vector injections (AAV2-OX1R or AAV2-GFP) into the PVN.
• Arterial blood pressure (ABP) and heart rate (HR) were monitored via radiotelemetry for eight weeks.
• Renal sympathetic nerve activity (RSNA) and ABP responses to orexin A were assessed; ROS levels and gene expression were analyzed.

Main Results:

• PVN OX1R overexpression elevated mean ABP, water intake, and reactive oxygen species (ROS) levels.
• Orexin A induced exaggerated RSNA and pressor responses, which were blocked by an OX1R antagonist.
• Elevated plasma vasopressin and increased ROS in OX1R-positive neurons were observed, with in vitro studies showing enhanced neuronal excitability and ROS production.

Conclusions:

• Chronic PVN OX1R overexpression contributes to hypertension by inducing oxidative stress, sympathetic overactivity, and increased vasopressin.
• Targeting PVN OX1R signaling presents a potential therapeutic strategy for hypertension.