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Altered regulation of sympathetic nerve activity by the caudal ventrolateral medulla and nucleus tractus solitarius in obese Zucker rats
Author(s) -
Huber Domitila A.,
Schreihofer Ann M.
Publication year - 2010
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.24.1_supplement.809.6
Subject(s) - rostral ventrolateral medulla , glutamatergic , medulla oblongata , gabaergic , endocrinology , medicine , medulla , chemistry , inhibitory postsynaptic potential , muscimol , agonist , glutamate receptor , central nervous system , receptor
Obese Zucker rats (OZR) have higher sympathetic nerve activity (SNA) and arterial pressure (AP) compared to lean Zucker rats (LZR). The higher SNA in OZR is due to reduced GABAergic inhibition of rostral ventrolateral medulla (RVLM), the source of drive for SNA. Caudal ventrolateral medulla (CVLM) provides this inhibitory input to RVLM, and CVLM is driven by a glutamatergic input from nucleus tractus solitarius (NTS). We hypothesized the CVLM provides reduced tonic inhibition to RVLM in OZR due to a reduced glutamatergic drive from NTS. Adult male rats were anesthetized with urethane (1.5 g/kg, iv), ventilated, and paralyzed to record splanchnic SNA and AP. Compared to LZR (n=13), OZR (n=14) had higher SNA (2.7 ± 0.4 vs. 1.6 ± 0.2 μV, P < 0.05 ) and mean AP (130 ± 2 vs. 123 ± 2 mmHg, P < 0.05 ). Inhibition of glutamatergic inputs to CVLM (kynurenate; 5.4 nmol/100 nl) evoked smaller rises in SNA in OZR (n=7) vs. LZR (n=7; 169 ± 23 vs. 289 ± 17 %, P < 0.05 ). This was not due to a reduced ability of GABA to inhibit RVLM because injections of GABA into RVLM (0.3, 1.0, 3.0 nmol) evoked comparable decreases in SNA in OZR (n=7) and LZR (n=7). Inhibition of NTS (muscimol; 100 pmol) evoked smaller rises in SNA in OZR (n=7) vs. LZR (n=6; 62 ± 11 vs. 112 ± 14 %, P < 0.05 ). These results suggest higher SNA in OZR may be due to reduced tonic GABA from CVLM. Further, reduced glutamatergic inputs from NTS to CVLM may contribute to diminished inhibition from CVLM to RVLM in OZR. Grant Support: NIH R01HL086759