FIG. 4.

Feed-forward induction of oxidative stress and nuclear factor-κB (NF-κB) activation in the paraventricular nucleus (PVN) during angiotensin II-dependent hypertension. Systemic angiotensin II infusion modeling activation of the renin-angiotensin system raises blood pressure and induces subunits of the NADPH oxidase complex in cells of the PVN within the hypothalamus. Superoxide generation within the PVN triggers phosphorylation of regulators and subunits of the NF-κB signaling complex. Free to translocate from the cytoplasm to the nucleus of the cell, NF-κB induces transcription of inflammatory cytokines, including TNF-α and interleukin-1β (IL-1β) that drive sympathetic outflow from the central nervous system and further elevate blood pressure, sustaining a prohypertensive, proinflammatory cycle.