Angiotensin II slow-pressor hypertension enhances NMDA currents and NOX2-dependent superoxide production in hypothalamic paraventricular neurons.

Am J Physiol Regul Integr Comp Physiol. 2013 Jun 15;304(12):R1096-106. Wang G1, Coleman CG, Chan J, Faraco G, Marques-Lopes J, Milner TA, Guruju MR, Anrather J, Davisson RL, Iadecola C, Pickel VM. “Adaptive changes in glutamatergic signaling within the hypothalamic paraventricular nucleus (PVN) may play a role in the neurohumoral dysfunction underlying the hypertension induced by "slow-pressor" ANG II infusion”. To test their hypothesis, the authors performed several elegant experiments. In experiment 1, the authors used electron microscope immunolabelling to show that in the PVN dendrities of ang II infused mice, there was colocalization of NOX2 and N-methyl-D-aspartate receptor (NMDAR) NR1 subunits. In experiment 2, there was increased reactive oxygen species but decreased nitric oxide (NO) production at baseline and after NMDA administration in cells isolated from ang II infused mice. In experiment 3, NMDA induced increases in inward current shown by whole cell recording in spinally projecting PVN cells in slices was reversed by ROS scavenger and NO donor in ang II group. These experiments clearly demonstrated the relationship between enhanced glutamatergic signaling in the PVN and other well-known mechanisms that are involved in the development of ang II slow-pressor hypertension.-Madhan