Non-NMDA receptors mediate both pressor and depressor actions of the cardiovascular-reactive areas in the brainstem of cats.
L-glutamate (Glu), an important excitatory transmitter in the central nervous system, is mainly mediated via two kinds of ionotropic Glu receptors: N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)/kainate (non-NMDA) receptors. Microinjection of Glu (0.1 M, 30 nL) into gigantocellular tegmental field (FTG), dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) induced increases of the systemic arterial pressure (SAP) and the sympathetic vertebral nerve activities (VNA), while its microinjection into caudal ventrolateral medulla (CVLM) induced decreases of SAP and VNA. In this study, the 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA antagonist, was used to examine the effects of non-NMDA receptors on Glu-induced cardiovascular responses. Cats were anesthetized intraperitoneally with a mixture of urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) and paralyzed with gallamine triethiodide (4 mg/kg, i.v. per hour). CNQX blocked the Glu-induced pressor responses in FTG, DM and RVLM but potentiated the depressor responses in CVLM. These results suggest that non-NMDA receptors modulate the central pressor and depressor responses in an opposite direction. On the other hand, activation of DM and RVLM neurons by application of AMPA (5 mM, 30 nL) evoked pressor responses. These AMPA-induced responses were significantly blocked by CNQX. Interestingly, CNQX itself induced pressor responses in many stimulated points of the pressor areas (FTG: 6/9; DM: 13/24; RVLM: 6/13), indicating a tonic release of Glu mediating depressor effects. In conclusion, non-NMDA receptors within the pressor (FTG, DM and RVLM) and depressor (CVLM) areas may play different modulatory roles in cardiovascular integration. The depressor mechanism mediated by non-NMDA receptors is tonically activated by the release of endogenous Glu in these pressor and depressor areas.
Chen
S Y
SY
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Chai
C Y
CY
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002415:Cats; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid