Cytokines in the Hypothalamic Paraventricular Nucleus (PVN) are Not Required for Maintenance of Angiotensin II‐Salt Hypertension

Abstract

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)