Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat

• Published in: Pflügers Archiv 2024-11, Vol.476 (11), p.1677-1691
• Main Authors: Issotina Zibrila, Abdoulaye, Zhou, Jun, Wang, Xiaomin, Zeng, Ming, Ali, Md. Ahasan, Liu, Xiaoxu, Alkuhali, Asma A., Zeng, Zhaoshu, Meng, Yuan, Wang, Zheng, Li, Xuelan, Liu, Jinjun
• Format: Article
• Language: English
• Subjects: Angiotensin AT1 receptors; Angiotensin II; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Astrocytes; Biomedical and Life Sciences; Biomedicine; Blood pressure; Blood Pressure - drug effects; Cell Biology; Female; Human Physiology; Hypertension; Hypertension - metabolism; Hypertension - physiopathology; Hypothalamus; Immunofluorescence; Integrative Physiology; Ischemia; Ischemia - metabolism; Localization; Losartan - pharmacology; Microglia; Molecular Medicine; NAD(P)H oxidase; Neurosciences; NF-κB protein; NOX4 protein; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Placenta; Placenta - drug effects; Placenta - metabolism; Pre-eclampsia; Pre-Eclampsia - metabolism; Pre-Eclampsia - physiopathology; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptors; Tyrosine 3-monooxygenase; Up-Regulation; Western blotting
• ISSN: 0031-6768; 1432-2013; 1432-2013
• DOI: 10.1007/s00424-024-03010-2

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated ( p