Cardiovascular response to group I metabotropic glutamate receptor activation in NTS.
Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus tractus solitarius (NTS). Exogenous glutamate in the NTS activates neurons through ionotropic and metabotropic glutamate receptors (mGluRs). This study tested the hypothesis that group I mGluRs in the NTS produce depressor, bradycardic, and sympathoinhibitory responses. In urethan-anesthetized rats, unilateral 30-nl microinjections of the group I-selective mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The dose of drug that produced 50% of the maximal response (ED50) was 50-100 microM. The response to microinjection of equal concentrations of DHPG or the general mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) produced similar cardiovascular effects. The cardiovascular response to injection of DHPG or ACPD was abolished by NTS blockade of mGluRs with alpha-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid did not attenuate the response to DHPG or ACPD injection. These data suggest that DHPG and ACPD activate mGluRs in the NTS and do not require ionotropic glutamate receptors to produce their cardiovascular response. In the NTS the group I mGluRs produce responses that are consistent with excitation of neurons involved in reducing sympathetic outflow, heart rate, and arterial pressure.
Foley
C M
CM
Department of Veterinary Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
Vogl
H W
HW
Mueller
P J
PJ
Hay
M
M
Hasser
E M
EM
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*
D001565:Benzoates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D008734:Methoxyhydroxyphenylglycol; D016202:N-Methylaspartate; D007736:Kynurenic Acid; D007608:Kainic Acid; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol