Ang II-salt hypertension depends on neuronal activity in the hypothalamic paraventricular nucleus but not on local actions of tumor necrosis factor-α

Megan E. Bardgett, Walter W. Holbein, Myrna Herrera-Rosales, Glenn M. Toney

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Development of angiotensin II (Ang II)-dependent hypertension involves microglial activation and proinflammatory cytokine actions in the hypothalamic paraventricular nucleus (PVN). Cytokines activate receptor signaling pathways that can both acutely grade neuronal discharge and trigger long-term adaptive changes that modulate neuronal excitability through gene transcription. Here, we investigated contributions of PVN cytokines to maintenance of hypertension induced by subcutaneous infusion of Ang II (150 ng/kg per min) for 14 days in rats consuming a 2% NaCl diet. Results indicate that bilateral PVN inhibition with the GABA-A receptor agonist muscimol (100 pmol/50 nL) caused significantly greater reductions of renal and splanchnic sympathetic nerve activity (SNA) and mean arterial pressure in hypertensive than in normotensive rats (P<0.01). Thus, ongoing PVN neuronal activity seems required for support of hypertension. Next, the role of the prototypical cytokine tumor necrosis factor-α was investigated. Whereas PVN injection of tumor necrosis factor-α (0.3 pmol/50 nL) acutely increased lumbar and splanchnic SNA and mean arterial pressure, interfering with endogenous tumor necrosis factor-α by injection of etanercept (10 μg/50 nL) was without effect in hypertensive and normotensive rats. Next, we determined that although microglial activation in PVN was increased in hypertensive rats, bilateral injections of minocycline (0.5 μg/50 nL), an inhibitor of microglial activation, failed to reduce lumbar or splanchnic SNA or mean arterial pressure in hypertensive or in normotensive rats. Collectively, these findings indicate that established Ang II-salt hypertension is supported by PVN neuronal activity, but short term maintenance of SNA and arterial blood pressure does not depend on ongoing local actions of tumor necrosis factor-α.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalHypertension
Volume63
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • blood pressure
  • cytokines
  • inflammation

ASJC Scopus subject areas

  • Internal Medicine

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