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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

Department of Human Physiology, School of Medicine, Flinders University, Bedford Park, South Australia, Australia

Submitted 18 August 2004 ; accepted in final form 10 November 2004

Neurons in the rostral medullary raphé/parapyramidal region regulate cutaneous sympathetic nerve discharge. Using focal electrical stimulation at different dorsoventral raphé/parapyramidal sites in anesthetized rabbits, we have now demonstrated that increases in ear pinna cutaneous sympathetic nerve discharge can be elicited only from sites within 1 mm of the ventral surface of the medulla. By comparing the latency to sympathetic discharge following stimulation at the ventral raphé site with the corresponding latency following stimulation of the spinal cord [third thoracic (T3) dorsolateral funiculus] we determined that the axonal conduction velocity of raphé-spinal neurons exciting ear pinna sympathetic vasomotor nerves is 0.8 ± 0.1 m/s (n = 6, range 0.6–1.1 m/s). Applications of the 5-hydroxytryptamine (HT)_2A antagonist trans-4-((3Z)3-[(2-dimethylaminoethyl)oxyimino]-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate (SR-46349B, 80 µg/kg in 0.8 ml) to the cerebrospinal fluid above thoracic spinal cord (T1-T7), but not the lumbar spinal cord (L2-L4), reduced raphé-evoked increases in ear pinna sympathetic vasomotor discharge from 43 ± 9 to 16 ± 6% (P < 0.01, n = 8). Subsequent application of the excitatory amino acid (EAA) antagonist kynurenic acid (25 µmol in 0.5 ml) substantially reduced the remaining evoked discharge (22 ± 8 to 6 ± 6%, P < 0.05, n = 5). Our conduction velocity data demonstrate that only slowly conducting raphé-spinal axons, in the unmyelinated range, contribute to sympathetic cutaneous vasomotor discharge evoked by electrical stimulation of the medullary raphé/parapyramidal region. Our pharmacological data provide evidence that raphé-spinal neurons using 5-HT as a neurotransmitter contribute to excitation of sympathetic preganglionic neurons regulating cutaneous vasomotor discharge. Raphé-spinal neurons using an EAA, perhaps glutamate, make a substantial contribution to the ear sympathetic nerve discharge evoked by raphé stimulation.

5-hydroxytryptamine_2A receptors; kynurenic acid; SR-46349B; sympathetic preganglionic neuron; cutaneous blood flow

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