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N‐Methyl‐D‐Aspartate (NMDA) Receptors Contribute to the Excitatory Sympathetic and Hemodynamic Responses to Blood‐borne Pro‐inflammatory Cytokines in Rat
Author(s) -
Wei ShunGuang,
Yu Yang,
Felder Robert
Publication year - 2015
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.29.1_supplement.987.3
Subject(s) - nmda receptor , medicine , glutamate receptor , endocrinology , excitatory postsynaptic potential , receptor , tumor necrosis factor alpha , blood pressure , proinflammatory cytokine , hemodynamics , sympathetic nervous system , pharmacology , inflammation
Pro‐inflammatory cytokines (PICs) have been implicated in the pathophysiology of hypertension (HTN) and heart failure (HF). The PICs tumor necrosis factor‐a (TNF‐a) and interleukin‐1b (IL‐1b) act within the brain to increase blood pressure (BP, mmHg), heart rate (HR, bpm) and renal sympathetic nerve activity (RSNA, %). However, the mechanisms by which PICs activate sympathetic drive to regulate cardiovascular function remain unclear. Evidence suggests that PICs can potentiate glutamate‐mediated neuronal excitation by increasing local glutamate concentrations and modulating NMDA and GABA receptor function in the CNS. In this study, we examined whether NMDA receptors contribute to the central excitatory effects of blood‐borne PICs. In urethane‐anesthetized SD rats,an intracarotid artery injection of TNF‐α (200 ng,n=5) or IL‐1β (200 ng, n=5), targeting the forebrain, significantly (* p<0.01, versus baseline) increased BP (21.8 ± 1.9* and 23.3 ± 2.1*), HR (61 ± 7* and 68 ± 7*) and integrated RSNA (85.6 ± 4.5* and 91.6 ± 4.7*, respectively). A concurrent continuous intracerebroventricular infusion of the NMDA antagonist AP5 (20 µg over 60 min) significantly (†p<0.01, versus PIC alone) attenuated TNF‐α or IL‐1β induced pressor responses on BP (9.1 ± 1.9†and 11.0 ± 2.1†), HR (18 ± 4†and 20 ± 5†) and RSNA (48.5 ± 3.1†and 46.6 ± 3.5†, respectively). These data suggest that increased activation of NMDA receptors plays an important role in mediating the central effects of circulating PICs on sympathetic drive and cardiovascular function in inflammatory conditions such as HTN and HF.