Figure 1. Proposed hypothesis of a dysfunctional autonomic-immune-vascular mechanism in neurogenic hypertension.

A coordinated peripheral-brain communication is critical in the development and establishment of neurogenic hypertension. AT1 receptors on SFO/OVLT and other CVOs are activated by increased plasma Ang II and an integrated signal is transmitted to the PVN. This results in the activation of microglia and increased generation of ROS and cytokines and decrease in NO. This leads to increased neuronal activity by regulation of ion channel function directly or indirectly. Ang II generated within the PVN can also activate neuronal AT1 receptors to compliment changes in neuronal activity. An imbalance in sympathetic/parasympathetic activities can directly influence bone marrow activity resulting in increase in pro-inflammatory cells (PICs, increase inflammation) and decrease in EPCs (decrease in vascular repair). All these events would lead to high BP and associated CV pathophysiology. These neural-vascular signals are further perpetuated by AT1 receptor-mediated changes in cerebral blood vessels, interrupting the integrity of BBB and allowing inflammatory cells to enter the brain parenchyma, contributing to microglial activation and inflammation in the PVN. A similar AT1-dependent mechanism may be present in other cardioregulatory brain regions such as the NTS and the RVLM.