2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and Hypertension

Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit hyperactivity disorder (ADHD) since SHR display the major symptoms of ADHD (hyperactivity, impulsivity, inablity to sustain attention during behavioral tasks). We previously showed that electrical and/or K+-stimulated release of dopamine (DA) from nerve terminals in the prefrontal cortex, nucleus accumbens, and caudate-putamen of SHR was significantly lower than that of Wistar-Kyoto (WKY) control rats. The aim of the present investigation was to determine whether glutamate-stimulated release of DA from nucleus accumbens core and shell of SHR was significantly different from that of WKY. Using an in vitro superfusion technique, we showed that glutamate-stimulated release of [3H]DA from striatal slices is mediated by glutamate activation of AMPA receptors and that glutamate-stimulated release of [3H]DA from nucleus accumbens core and shell of 4-6-week-old SHR and WKY is not significantly different. Glutamate-stimulated release of [3H]DA from SHR shell is significantly lower than SHR core and there is also a tendency for glutamate-stimulated [3H]DA release from SHR shell to be lower than release from WKY shell.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Dopamine; Excitatory Amino Acid Antagonists; Glutamic Acid; Hypertension; In Vitro Techniques; Nucleus Accumbens; Perfusion; Quinoxalines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, AMPA

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.

Topics: 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Blood Pressure; Consciousness; Excitatory Amino Acid Antagonists; Heart Rate; Hypertension; Male; N-Methylaspartate; Phenylephrine; Quinoxalines; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Reflex; Spinal Cord