Modulation of peripheral sympathetic nerve transmission

Gary S. Francis

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


The past 15 years have been witness to a remarkable growth in knowledge regarding the modulation of "sympathetic traffic" to neuroeffector organs, including vascular tissue. The release of norepinephrine from peripheral sympathetic neurons is now known to be under both negative and positive feedback control. Norepinephrine, when released from peripheral neurons, acts on presynaptic alpha2-receptors to inhibit further neurotransmission. Vascular postsynaptic alpha2-receptors, sensitive to circulating catecholamines, subserve vasoconstriction. The antihypertensive agents clonidine, guanabenz and guanfacin likely reduce blood pressure by acting centrally on alpha2 postsynaptic neurons to limit sympathetic transmission to blood vessels. Clonidine can produce venoconstriction and thereby improve orthostatic hypotension by activating venous alpha2-receptors. Additional presynaptic dopaminergic receptors (DA2), muscarinic receptors (acetylcholine), opioid receptors, prostaglandin receptors, adenosine receptors (A1) and histamine (H2) receptors are present on sympathetic nerve membranes and, when engaged with the appropriate ligand, can limit the exocytotic process. Gamma-aminobutyric acid and serotonin demonstrate similar roles in reducing sympathetic nerve activity. In contrast to these inhibitory presynaptic mechanisms, facilitation of norepinephrine release appears to occur by way of neuronal angiotensin II receptor activation and perhaps through stimulation of sympathetic nerve membrane beta2-receptors. An appreciation of these inhibitory and facilitator mechanisms is useful in the treatment of a variety of clinical conditions, including hypertension, heart failure, orthostatic hypotension, septic shock and a number of common withdrawal syndromes.

Original languageEnglish (US)
Pages (from-to)250-254
Number of pages5
JournalJournal of the American College of Cardiology
Issue number1
StatePublished - Jul 1988
Externally publishedYes


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