3032005

Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats.

Article date: 2008/9/2

PubMed ID: 3032005

Journal name: American journal of physiology. Heart and circulatory physiology (ISSN: 0363-6135)

DOI: 10.1152/ajpheart.216.2008

ABSTRACT

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (<50 mmHg) and increased SNA to 209+/-22% (P<0.05), but the subsequent inhibition of the NTS by microinjection of the GABA(A) agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274+/-54%; P<0.05; n=7). In vagotomized rats with baroreceptors unloaded, inhibition of glutamatergic inputs to CVLM evoked a larger rise in SNA when central respiratory drive was increased (219+/-16% vs. 271+/-17%; n=5; P<0.05). These data suggest that baroreceptor inputs provide the major drive for the NTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive.

Author List: Mandel Daniel A, Schreihofer Ann M

Publication Types: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Article Date: 2008/08/29

Substances mentioned in the article: Excitatory Amino Acid Antagonists; GABA Agonists; Glutamine; Nitroprusside; Muscimol; Kynurenic Acid;

Mesh terms: Animals; Baroreflex; Blood Pressure; Blood Vessels/innervation; Disease Models, Animal; Excitatory Amino Acid Antagonists/administration & dosage; GABA Agonists/administration & dosage; Glutamine/antagonists & inhibitors; Hypotension/chemically induced; Kynurenic Acid/administration & dosage; Male; Medulla Oblongata/cytology; Microinjections; Muscimol/administration & dosage; Neural Inhibition/drug effects; Neural Pathways/metabolism; Neurons/metabolism; Nitroprusside; Rats; Rats, Sprague-Dawley; Respiratory Center/metabolism; Solitary Nucleus/cytology; Splanchnic Nerves/metabolism; Sympathetic Nervous System/drug effects; Time Factors; Vagotomy;

Citations: - 3567646

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