Although the rostral ventrolateral medulla maintains neurogenic vasomotor tone via glutamatergic excitation to sympathetic preganglionic neurons located at the intermediolateral cell column (IML) of thoracic spinal cord, the relative contribution of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on IML neurons at rest or during endotoxemia remain unknown. The present study addressed this issue using a combination of physiological, pharmacological, and double-immunofluorescence approaches. Adult male Sprague-Dawley rats maintained under propofol anesthesia were used. Intrathecal administration of equimolar concentrations (75, 150, or 300 nmol) of an NMDA antagonist, dizocilpine (MK801), or a non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into T10 to T12 spinal cord elicited a reduction in resting vasomotor tone that was comparable in time course and in magnitude. Although both glutamate receptor antagonists exacerbated mortality and potentiated the elicited hypotension, bradycardia, or reduction in vasomotor tone during experimental endotoxemia induced by intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg; results comparable to 6-cyano-7-nitroquinoxaline-2,3-dione at 150 nmol) were obtained only when MK801 was given at 300 nmol. Confocal microscopy further showed that augmented immunoreactivity of NR1 subunit on IML neurons coincided with the phase of endotoxemia when vasomotor tone was augmented; GluR1 immunoreactivity remained stable throughout experimental endotoxemia. These findings suggest that NMDA and non-NMDA receptors on IML neurons contribute to the generation of resting sympathetic vasomotor tone. However, up-regulation of NMDA receptors on IML neurons plays a crucial role in the maintenance of vasomotor tone during endotoxemia.
|Number of pages||7|
|Publication status||Published - 2006 Oct 1|
All Science Journal Classification (ASJC) codes
- Emergency Medicine
- Critical Care and Intensive Care Medicine