Respiratory modulation of sympathetic nerve activity: effect of MK-801.
The modulation of splanchnic sympathetic nerve activity (SNA) by brain stem neural networks generating the respiratory rhythm was examined in decerebrate, unanesthetized, vagotomized, artificially ventilated rats before and after blockade of the N-methyl-D-aspartate (NMDA) channel with intravenous administration of dizocilpine (MK-801). NMDA channel blockade 1) prolonged inspiration and reduced the phrenic nerve amplitude, 2) reduced SNA to 40% of control levels, and 3) decreased mean arterial pressure by 20 mmHg. A strong synchronization of SNA to the central respiratory cycle (monitored by the activity on the phrenic nerve) was maintained after MK-801 administration, although a brief inhibition of SNA during early inspiration and a sympathetic excitation during early expiration were eliminated. These results suggest 1) the existence of an NMDA-independent mechanism by which some elements of the brain stem respiratory network excite sympathetic outflow, 2) that the NMDA-mediated influence of specific classes of brain stem respiratory neurons can modulate this excitation during portions of the respiratory cycle, and 3) that an NMDA-dependent excitation in the brain stem or spinal cord plays a significant role in maintaining basal levels of splanchnic SNA.
Morrison
S F
SF
Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology*
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate