Figure 3. Pro-inflammatory hypertensive signalling in the hypothalamus.

In response to overnutrition states, pro-inflammatory signalling including IKKβ/NFκB is activated in certain hypothalamic neurons such as POMC neurons in the ARC. NFκB activation triggers a variety of molecular reactions, such as increased levels of SOCS3 and of PTP1b, contributing to SNS activation and subsequent increased blood pressure. In addition, POMC neurons bind TNFα, which further stimulates SNS activation. Also, TNFα and IL-1β activate perivascular macrophages that produce prostaglandin E2, which signals through the PVN to activate the SNS and subsequent hypertension. Central RAS activation and Ang II production stimulates IKKβ/NFκB activation and ROS production in PVN neurons. Subsequent release of pro-inflammatory cytokines further contributes to ROS production, mitochondrial dysfunction, neuroinflammation and sustained increase in blood pressure leading to pathological hypertension.