Spinal cord excitatory amino acids and cardiovascular autonomic responses

The excitatory amino acid subtype receptor agonists, N-methyl-D-aspartate (NMDA) and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, a non-NMDA agonist), produce specific dose-related heart rate and vasoconstrictor responses when given by injection into the upper thoracic or lumbar intrathecal space of the conscious rabbit. The responses are inhibited by prior intrathecal injection of the specific excitatory amino acid subtype receptor antagonist, 2-amino-5-phosphonovaleric acid (AP-5) or 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. Baroreceptor heart rate reflex function is inhibited by AP-5 and by DNQX applied to the upper thoracic spinal cord. In contrast baroreflex vasoconstrictor function is blocked by AP-5 but not by DNQX given in the lumbar intrathecal space. The experiments support previous evidence that spinal excitatory amino acids are important as neurotransmitters at the level of the sympathetic preganglionic neuron and as such exert tonic and reflex control of autonomic cardiovascular function. It is concluded that 1) intrathecal activation of NMDA and non-NMDA subtype receptors has similar but independent effects on heart rate and on blood pressure and 2) NMDA receptors alone participate in mediation of baroreflex vasoconstrictor function, whereas both sets of receptors determine reflex sympathetic heart rate effects.