Glucocorticoids reduce responses to AMPA receptor activation and blockade in nucleus tractus solitarius.
We tested the hypothesis that glucocorticoids attenuate changes in arterial pressure and renal sympathetic nerve activity (RSNA) in response to activation and blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors within the nucleus of the solitary tract (NTS). Experiments were performed in Inactin-anesthetized male Sprague-Dawley rats treated for 7 +/- 1 days with a subcutaneous corticosterone (Cort) pellet or in control rats. Baseline mean arterial pressure (MAP) was significantly higher in Cort-treated rats (109 +/- 2 mmHg, n = 39) than in control rats (101 +/- 1 mmHg, n = 48, P < 0.05). In control rats, microinjection of AMPA (0.03, 0.1, and 0.3 pmol/100 nl) into the NTS significantly decreased MAP at all doses and decreased RSNA at 0.1 and 0.3 pmol/100 nl. Responses to AMPA in Cort-treated rats were attenuated at all doses of AMPA (P < 0.05). Responses to the AMPA-kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were also significantly reduced in Cort-treated rats relative to control rats. Blockade of glucocorticoid type II receptors with mifepristone significantly enhanced responses to CNQX in both control and Cort rats. We conclude that glucocorticoids attenuate MAP and RSNA responses to activation and blockade of AMPA receptors in the NTS.
Shank
Sylvan S
SS
Department of Pharmacology, The University of Missouri, 2411 Holmes Street, Kansas City, MO 64108, USA.
Scheuer
Deborah A
DA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology*; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D018091:Receptors, AMPA; D015735:Mifepristone; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D003345:Corticosterone