Role of neurotransmitters in the central regulation of the cardiovascular system.
The last decade has seen tremendous progress in determining the nature of the neurotransmitters which regulate central nervous system pathways involved in the regulation of blood pressure. Investigations are now pursuing the identity and functional importance of neurotransmitters contained within pathways shown to be important in cardiovascular regulation. In addition, several key components of the brain stem networks involved in the control of sympathetic activity have been identified. For example, numerous studies indicate the importance of neurons located in the rostral ventrolateral medulla in the regulation of SPN. Indeed, this area contains medullospinal sympathoexcitatory neurons which represent the final site of integration of many brain stem and reflex pathways involved in the regulation of sympathetic nerve activity. The neurotransmitter which is utilized by this medullospinal pathway remains unknown. Epinephrine, substance P and glutamate have all been hypothesized as primary chemical mediators in the descending pathway from the brain stem to SPN. Interestingly, lesions of, or antagonists to, epinephrine, substance P, glutamate and 5-HT neurons all abolish sympathetic activity and reduce blood pressure to a level similar to that in a spinal animal. Clearly, not all these transmitters are primary mediators of sympathetic information carried from the brain stem to the spinal cord. It is likely that monoamines and neuropeptides act in the IML, as in other area of the central nervous system, as neuromodulators to set the level of excitability of SPN rather than relaying sympathetic information over a functionally specific medullospinal pathway. This conclusion is supported by the observation that midline medullary 5-HT neurons provide a tonic excitatory input to SPN, but receive no afferent inputs from other central sympathetic or baroreceptor pathways. However, the firing of 5-HT neurons appears to relate to the state of vigilance of the animal. This suggests that 5-HT neurons may lower the threshold of SPN to sympathetic inputs during states of wakefulness. In addition, the time course of the norepinephrine-mediated slow EPSPs and IPSPs in SPN is consistent with a gain-setting function. By analogy, epinephrine is likely to act as a neuromodulator in the IML rather than to serve as the primary mediator of sympathetic information descending from the rostral ventrolateral medulla.(ABSTRACT TRUNCATED AT 400 WORDS)
McCall
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RB
Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
D000818:Animals; D001921:Brain / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000294:innervation; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology*
D018377:Neurotransmitter Agents