Author + information
- Received October 26, 1987
- Revision received January 20, 1988
- Accepted February 2, 1988
- Published online July 1, 1988.
- Gary S. Francis, MD, FACC∗
- ↵∗Address for reprints: Gary S. Francis, MD, Cardiovascular Research (111C1). Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
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 alpha2postsynaptic 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.
☆ This study was supported by the Veterans Administration Research Service, Washington, D.C. and Grants HL22977, HL32427, HL07184 and RR-400 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
- Received October 26, 1987.
- Revision received January 20, 1988.
- Accepted February 2, 1988.