Angiotensin II-induced hypertension is modulated by nuclear factor-κBin the paraventricular nucleus

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Hypertension is considered a low-grade inflammatory condition, and understanding the role of transcription factors in guiding this response is pertinent. A prominent transcription factor that governs inflammatory responses and has become a focal point in hypertensive research is nuclear factor-κB (NFκB). Within the hypothalamic paraventricular nucleus (PVN), a known brain cardioregulatory center, NFκB becomes potentially even more important in ultimately coordinating the systemic hypertensive response. To definitively demonstrate the role of NFκB in the neurogenic hypertensive response, we hypothesized that PVN NFκB blockade would attenuate angiotensin II-induced hypertension. Twelve-week-old male Sprague-Dawley rats were implanted with radiotelemetry probes for blood pressure measurement and allowed a 7-day recovery. After baseline blood pressure recordings, rats were administered either continuous NFκB decoy oligodeoxynucleotide infusion or microinjection of a serine mutated adenoviral inhibitory-κB vector, or their respective controls, bilaterally into the PVN to inhibit NFκB at two levels of its activation pathway. Simultaneously, rats were implanted subcutaneously with an angiotensin II or saline-filled 14-day osmotic minipump. After the 2-week treatments, rats were euthanized and brain tissues collected for PVN analysis. Bilaterally inhibited NFκB rats had a decrease in blood pressure, NFκB p65 subunit activity, proinflammatory cytokines, and reactive oxygen species, including the angiotensin II type 1 receptor, angiotensin-converting enzyme, tumor necrosis factor, and superoxide in angiotensin II-treated rats. Moreover, after NFκB blockade, key protective antihypertensive renin-angiotensin system components were upregulated. This demonstrates the important role that transcription factor NFκB plays within the PVN in modulating and perpetuating the hypertensive response via renin-angiotensin system modulation.

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Hypertension (Dallas, Tex. : 1979)

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