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Role of Brain Angiotensin II, Nitric Oxide and Reactive Oxygen Species in Blood Pressure Control: The Importance in Contrasting Forms of Hypertension

Sympathetic nervous system has a crucial role in both human and experimental hypertension. Major centers of sympathetic outflow and blood pressure (BP) control are located in hypothalamic paraventricular nucleus (PVN) and brainstem nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM). Angiotensin II (ANG II), nitric oxide (NO) and reactive oxygen species (ROS) acting in PVN, NTS or RVLM contribute to sympathoexcitation. Aim of our project is to evaluate the interactions of these systems in brain control of BP in rats or mice with ANG II-dependent or NO-deficient hypertension that are characterized by sympathetic hyperactivity. Unique MRI/DTI system will be used for evaluation of the connectivity of brain nuclei responsible for sympathoexcitation in these hypertensive models. Chronic intracerebroventricular or systemic blockades of the above systems (losartan, L-NAME or tempol) will be studied in animals with established or developing hypertension. Better understanding of central interaction of these systems may improve therapeutic strategies in human hypertension.