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Glutamatergic Receptor Activation in the Rostral Ventrolateral Medulla Contributes to the Sympathoexcitatory Response of Hyperinsulinemia
Author(s) -
Bardgett Megan Elyse,
Stocker Sean D
Publication year - 2009
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.23.1_supplement.958.16
Subject(s) - hyperinsulinemia , rostral ventrolateral medulla , medicine , endocrinology , glutamatergic , glutamate receptor , ionotropic effect , kynurenic acid , blood pressure , chemistry , insulin , receptor , insulin resistance , heart rate
Hyperinsulinemia increases sympathetic nerve activity (SNA) and has been linked to cardiovascular morbidity in obesity. Many sympathoexcitatory responses are mediated by glutamatergic receptor activation of spinally projecting neurons in the RVLM. Therefore, we hypothesized that ionotropic glutamate receptors in the RVLM contribute to elevated SNA during hyperinsulinemia. Hyperinsulinemic‐euglycemic clamps were performed in urethane‐anesthetized, male Sprague‐Dawley rats (270‐350g, n=8) by IV infusion of insulin (7.5 mU/kg/min) and 50% dextrose (.25‐.75 ml/hr) for 120 min. After 90 min, hyperinsulinemic clamps significantly increased plasma insulin (2.5±0.9 to 12.2±3.9 ng/ml, P<0.05), elevated lumbar (125±18%, P<0.01) and renal SNA (48±17%, P<0.05) without any significant change in arterial blood pressure (0 min: 125±3 vs 90 min: 118±4 mmHg) or plasma glucose levels (0 min: 107±9 vs 90 min: 111±10 mg/dl). RVLM injection of the glutamate receptor antagonist kynurenic acid (5 nmol/60 nL/ side, n=4) vs saline (n=4) significantly reduced lumbar SNA (‐41±1% vs 3±1%, P<0.01) but did not significantly alter renal SNA (27±14% vs 0±3%) or arterial blood pressure (1±2 vs ‐1±1 mmHg). These findings indicate that hyperinsulinemia increases lumbar SNA, in part, through glutamatergic receptor activation in the RVLM. Supported by NIH HL090826 , AHA 0630202N & 0815372D