Glutamate, NMDA and NMDA receptor antagonists: cardiovascular effects of intrathecal administration in the rat

Hong, Yanguo; Henry, James L.

doi:10.1016/0006-8993(92)90366-h

Cited by 38 publications

(17 citation statements)

References 31 publications

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“…In anesthetized rats, i.t. AP-5 (200 nmol) decreases arterial pressure by ϳ10 -20 mmHg, which lasts ϳ30 min (14). This is in agreement with results of our pilot studies in anesthetized rats with the same dose.…”

Section: Contribution Of Excitatory Amino Acid Receptor Subtypes To Tsupporting

confidence: 92%

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Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Veitenheimer

Osborn

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.

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Section: Contribution Of Excitatory Amino Acid Receptor Subtypes To Tsupporting

confidence: 92%

“…Doses for AP-5 (20 mM) and CNQX (5 mM) were based on published reports (11,14) and preliminary studies in two groups of isoflurane anesthetized rats. Anesthesia was used in these dosedetermining pilot studies because i.t.…”

Section: Comparison Of the Arterial Pressure And Hr Responses To Itmentioning

confidence: 99%

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Veitenheimer

Osborn

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…91 Intrathecal injection of NMDA receptor agonists had independent e ects on heart rate and blood pressure, and these e ects were blocked by the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (AP-5). 92,93 Acute SCI causes immediate mechanical damage to the microvasculature of the cord followed by a secondary injury to the vessels, such as vasospasm, the combination of which produces spinal cord ischemia which may be progressive. 8,37 After acute cord clip compression injury in the rat, the decrease in regional SCBF at the injury site begins almost immediately and continues for at least 24 h. In the rat, there is a direct linear dose response relationship between the severity of injury as represented by clip force and the ischemic response.…”

Section: Discussionmentioning

confidence: 99%

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Tator

1999

Spinal Cord

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Objectives: To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the e ects of pre-and posttreatment with MK801 on axonal function, spinal cord blood¯ow (SCBF) and cord water content were studied after acute SCI in rats. Methods: Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the ®rst infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1.5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted. Results: In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was signi®cantly lower than in the saline group. There were no di erences in SCBF or cord water content between the MK801 and saline groups. Conclusion: Pre-and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the ®rst time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in a erent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

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“…It has been shown that microinjection of glutamate and NMDA into the intermediolateral nucleus and intrathecal administrationof these amino acids increase blood pressure and heart rate, indicating that NMDA receptors mediate excitation of spinal sympathetic neurons in pathways to heart and vessels [4]. In addition, spinal non-NMDA receptors are also involved in activation of sympathetic output regulating the cardiovascular function [18].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, glutamate receptors play important roles in the central cardiovascular regulation [3][4][5]. According to results of biochemical, pharmacological, electrophysiological, and molecular studies, glutamate receptors are classified as ionotropic and metabotropic.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Responses to NMDA Injected into Nuclei of Hypothalamus or Amygdala in Conscious Rats

Gören

Akıcı²,

Berkman³

et al. 2000

Pharmacology

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The nuclei of hypothalamus and amygdala have been shown to be involved in the central cardiovascular homeostasis. Recent studies suggest that glutamate-containing neurons have an important role in the regulation of the central cardiovascular function. In this study, we demonstrate the roles of the central nucleus of the amygdala and the paraventricular nucleus of the amygdala and the paraventricular nucleus or the dorsomedial nucleus of the hypothalamus in N-methyl-D-aspartate (NMDA) induced blood pressure and heart rate changes in conscious Sprague-Dawley rats. Intracerebroventricular or parenchymal injections of NMDA evoke increases in arterial pressure. The NMDA-induced elevations in blood pressure are more prominent when NMDA is administered into the dorsomedial nucleus of the hypothalamus. Microinjections of NMDA into the dorsomedial hypothalamus exert significant heart rate increases, whereas NMDA when administered into the paraventricular nucleus of the hypothalamus or into the central nucleus of the amygdala has no significant effect on the heart rate. The dorsomedial nucleus of the hypothalamus is found to be the most effective site in this respect. The present study provides strong evidence for the tonic glutamatergic influence on blood pressure and heart rate via NMDA receptors located within the dorsomedial nucleus and to a lesser extent via those located within the paraventricular nucleus of the hypothalamus.

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Glutamate, NMDA and NMDA receptor antagonists: cardiovascular effects of intrathecal administration in the rat

Cited by 38 publications

References 31 publications

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats

Cardiovascular Responses to NMDA Injected into Nuclei of Hypothalamus or Amygdala in Conscious Rats

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