Role of spinal NMDA and AMPA receptors in episodic hypertension in conscious spinal rats.
The neurotransmitters mediating the spinal sympathetic reflexes that initiate episodic hypertension after spinal cord injury are unknown. We examined the role of glutamatergic transmission in these reflexes by testing effects of the N-methyl-D-aspartate (NMDA)-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzoquinone (NBQX) on the reflex hypertension caused by colon distension. Antagonists were administered intrathecally in conscious rats 1-2 days (acute, n = 10) or 15-16 days (chronic, n = 14) after cord transection at the fifth thoracic segment under barbiturate anesthesia. AP-5 blocked pressor responses to intrathecal NMDA but had no effect on responses to AMPA; similarly, NBQX blocked responses to AMPA but had no effect on responses to NMDA. Before antagonist injection, colon distension increased mean arterial pressure by 24 +/- 1 mmHg (from 100 +/- 3 mmHg) and by 37 +/- 2 mmHg (from 116 +/- 3 mmHg) in the acute and chronic groups, respectively. Pretreatment with AP-5 attenuated the pressor responses by 36 and 37% in these respective groups; pretreatment with NBQX attenuated them by 34 and 31%. These data suggest that both NMDA and AMPA receptors contribute to spinal viscerosympathetic transmission and initiation of episodic hypertension in conscious spinal rats.
Maiorov
D N
DN
John P. Robarts Research Institute, University of Western Ontario, London, Canada.
Krenz
N R
NR
Krassioukov
A V
AV
Weaver
L C
LC
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012018:Reflex; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D018340:Receptors, Adrenergic, alpha-1; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D010656:Phenylephrine; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid