Angiotensin II-Induced Hypertension Is Modulated by Nuclear Factor-kappa B in the Paraventricular Nucleus

作者：Cardinale Jeffrey P; Sriramula Srinivas; Mariappan Nithya; Agarwal Deepmala; Francis Joseph^*

来源：Hypertension, 2012, 59(1): 113-U282.

DOI：10.1161/HYPERTENSIONAHA.111.182154

• angiotensin II
• hypertension
• cytokines
• transcription factors
• superoxide

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-kappa B (NF kappa B). Within the hypothalamic paraventricular nucleus (PVN), a known brain cardioregulatory center, NF kappa B becomes potentially even more important in ultimately coordinating the systemic hypertensive response. To definitively demonstrate the role of NF kappa B in the neurogenic hypertensive response, we hypothesized that PVN NF kappa B 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 NF kappa B decoy oligodeoxynucleotide infusion or microinjection of a serine mutated adenoviral inhibitory-kappa B vector, or their respective controls, bilaterally into the PVN to inhibit NF kappa B 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 NF kappa B rats had a decrease in blood pressure, NF kappa B 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 NF kappa B blockade, key protective antihypertensive renin-angiotensin system components were upregulated. This demonstrates the important role that transcription factor NF kappa B plays within the PVN in modulating and perpetuating the hypertensive response via renin-angiotensin system modulation. (Hypertension. 2012;59:113-121.). Online Data Supplement

• 出版日期2012-1