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Cytokines in the Hypothalamic Paraventricular Nucleus (PVN) are Not Required for Maintenance of Angiotensin II‐Salt Hypertension
Author(s) -
Bardgett Megan,
Herrera-Rosales Myrna C.,
Toney Glenn M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.891.12
Subject(s) - medicine , endocrinology , microinjection , splanchnic , angiotensin ii , hypothalamus , chemistry , blood pressure , mean arterial pressure , splanchnic nerves , hemodynamics , heart rate , stimulation
Rats consuming high salt and treated with systemic angiotensin II (Ang II) develop neurogenic hypertension mediated by elevation of sympathetic nerve activity (SNA) derived from a forebrain‐hypothalamic circuit. Cytokines are proposed to increase SNA and arterial blood pressure (ABP) and we therefore sought to determine their role within PVN in maintenance of AngII+salt hypertension. We first focused on tumor necrosis factor α (TNFα), which was microinjected into the PVN (0.3 pmol in 50 nl/side) of anesthetized normotensive (NT, 0.4% NaCl diet, n=10) rats. Although this increased lumbar SNA (18±7%), splanchnic SNA (49±9%) and mean ABP (4±2 mmHg) compared to vehicle (P<0.05), interfering with TNFα binding by PVN injection of etanercept (20 μg in 100 nl/side) did not affect recorded variables either in NT rats or in Ang II (150 ng/kg/min, sc) + salt (2% NaCl diet) hypertensive (HT, n=12) rats. Given this apparent lack of TNFα “tone” in PVN, we next non‐selectively inhibited local cytokine release by microinjection of minocycline (1 μg in 100 nl/side). This too failed to alter lumbar SNA (HT: 13±9% vs NT: 0±3%), splanchnic SNA (HT: 12±4% vs NT: 6±2%) or mean ABP (HT: 3±2 mmHg vs NT: −1±1 mmHg) in NT or HT rats. These findings indicate that whereas TNFα can act in PVN to increase SNA; maintenance of Ang II‐salt hypertension does not depend on either PVN actions of TNFα or microglia derived cytokines. Support: HL102310 & HL 088052 (GMT)