Membrane trafficking of NADPH oxidase p47(phox) in paraventricular hypothalamic neurons parallels local free radical production in angiotensin II slow-pressor hypertension.

J Neurosci. 2013 Mar 6;33(10):4308-16. Coleman CG1, Wang G, Faraco G, Marques Lopes J, Waters EM, Milner TA, Iadecola C, Pickel VM. “NADPH oxidase-generated reactive oxygen species (ROS) are highly implicated in the development of angiotensin II (AngII)-dependent hypertension mediated in part through the hypothalamic paraventricular nucleus (PVN)”. The authors tested the role of vasopressin and non-vasopressin neurons in the production of ROS in the PVN of ang II slow-pressor hypertension model. In the first set of experiments, the authors used ROS imaging to first confirm the increased production of ROS in ang II slow-pressor mice. Then the authors examined the baseline and NMDA induced ROS levels in vasopressin and non-vasopressin cells. Interestingly they found increased ROS production in vasopressin cells after NMDA infusion in ang II groups, however in non vasopressin cells the levels were increased in both the ang II groups and control groups. In the second set of examined the authors used electron microscopic dual labeling for vasopressin and a NADPH oxidase subunit, that was important for the production of ROS. The immunolabeling for p47 phox was decreased in the plasma membrane and increased in membranes just beneath the plasmalemmal surface in vasopressin and non-vasopressin cells of ang II mice respectively. Based on these findings the authors arrive at an interesting conclusion suggesting that the membrane assembly of vasopressin and non-vasopressin cells were differentially affected in the PVN of ang II slow-pressor model offsetting the homeostatic control of blood pressure.-Madhan