Modulation of endotoxin-induced changes in hemodynamics and glucose metabolism by an N-methyl-D-aspartate receptor antagonist

Khalil A. Yousef, Charles H. Lang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Excitatory amino acids (EAAs) are the principal mediators of fast excitatory neurotransmission in the mammalian central nervous system. Previous studies have demonstrated that N-methyl-D-aspartate (NMDA), an EAA agonist, produces a stress response that mimics that observed in animals receiving lipopolysaccharide (LPS). The present investigation determined the role that NMDA receptors play in the hemodynamic, metabolic, and hormonal changes induced by LPS. Chronically catheterized fasted rats received LPS with or without prior injection of MK 801, an NMDA receptor antagonist. LPS produced a classical stress response characterized by hypotension, tachycardia, increased glucose flux, and elevated plasma levels of glucagon, corticosterone, and catecholamines. MK 801 (intravenously) prevented the tachycardia in response to LPS, but did not consistently alter the fall in arterial blood pressure. The NMDA receptor antagonist also blunted the early elevation in plasma epinephrine and norepinephrine levels seen in LPS-injected rats, and this was associated with a smaller increment in plasma glucose and lactate concentrations and glucose flux. To confirm that MK 801 was functioning by antagonizing NMDA receptors within the brain, a second group of rats received an intracerebroventricular injection of MK 801 prior to LPS. The central administration of MK 801 also attenuated the increase in heart rate. These results indicate that central NMDA receptor stimulation mediates the LPS-induced tachycardia and suggest that the partial inhibition of the glucose metabolic response to LPS by MK 801 resulted from the smaller increment in plasma catecholamines.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalShock
Volume1
Issue number5
DOIs
StatePublished - May 1994

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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