Inhibition of muscle sympathetic nerve activity in humans by arginine vasopressin
Open accessAbstract
Arginine vasopressin, a potent vasoconstrictor, does not raise arterial pressure in normal humans even at pathophysiological plasma levels. To examine whether the pressor effect of vasopressin in humans is buffered by baroreceptor reflex inhibition of sympathetic nerve activity, we recorded postganglionic muscle sympathetic nerve activity directly from the peroneal nerve in 12 normal men before, during, and after a 20-minute intravenous infusion of vasopressin, 4 ng/kg/min, that increased mean plasma concentrations from 6.2 +/- 0.6 to 320 +/- 68 (SE) pg/ml. During the first 5 minutes (n = 8), mean arterial pressure increased from 91 +/- 3 to 97 +/- 4 mm Hg (p less than 0.05) and integrated sympathetic nerve activity decreased from 271 +/- 45 to 156 +/- 33 units (p less than 0.05). At 15 minutes (n = 12), arterial pressure did not differ from control values whereas forearm vascular resistance fell (p less than 0.05) and central venous pressure and heart rate increased (p less than 0.05). Sympathetic nerve activity remained below control levels throughout the infusion (202 +/- 31 vs 254 +/- 40 units before infusion; p less than 0.05). An effect of vasopressin on ganglionic transmission was excluded, since the sympathoexcitatory response to apnea was not attenuated during vasopressin. Thus, pathophysiologic levels of vasopressin in humans cause inhibition of muscle sympathetic nerve activity that is not due to a ganglionic blocking action. The sympathoinhibition may be caused in part by the modest increases in mean arterial and central venous pressures and attendant stimulation of arterial and cardiac baroreceptors. The reflex decrease in sympathetic nerve activity would be expected to buffer the direct vasoconstrictor effects of vasopressin.
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Cites
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Claims the paper makes
4 of 10 cited sources checked · 4 supported · 0 flagged
- Premiseown data
AVP facilitated reflex forearm vasodilation during increases in venous return and central venous pressure produced by sudden release of lower body negative pressure.
“AVP facilitated reflex forearm vasodilation during increases in venous return and central venous pressure produced by sudden release of lower body negative pressure.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] 5. Aylward PE, Floras JS, Leimbach WN, Abboud FM. Effect of vasopressin on the circulation and its baroreflex control in normal humans. Circulation 1986;73:1145-1154 source
- Premisecitation
In normal subjects, AVP infused intravenously at 4 ng/kg/min decreased resting forearm vascular resistance.
“We have recently shown that AVP (4 ng/kg/min) infused intravenously in normal subjects decreased resting forearm vascular resistance.5”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] 5. Aylward PE, Floras JS, Leimbach WN, Abboud FM. Effect of vasopressin on the circulation and its baroreflex control in normal humans. Circulation 1986;73:1145-1154 source
- Findingown data
During the first 5 minutes of AVP infusion (n=8), mean arterial pressure increased from 91 ± 3 to 97 ± 4 mm Hg (p<0.05).
“During the first 5 minutes (n = 8), mean arterial pressure increased from 91 ± 3 to 97 ± 4 mm Hg (p<0.05)”
Quote in the paperSubstantial claim - Findingown data
AVP infusion at 4 ng/kg/min increased mean plasma AVP concentrations from 6.2 ± 0.6 to 320 ± 68 pg/ml in normal men.
“increased mean plasma concentrations from 6.2 ± 0.6 to 320 ± 68 (SE) pg/ml.”
Quote in the paperSubstantial claim - Findingown data
At 15 minutes of AVP infusion (n=12), arterial pressure did not differ from control values.
“At 15 minutes (n = 12), arterial pressue did not differ from control values”
Quote in the paperSubstantial claim
- Findingown data
In 12 subjects, SNA decreased abruptly from 254 ± 40 to 139 ± 27 units during initial AVP infusion.
“In 12 subjects SNA decreased abruptly from 254 ± 40 to 139 ± 27 units”
Quote in the paperSubstantial claim - Findingown data
At 15 minutes of AVP infusion (n=12), central venous pressure increased (p<0.05).
“central venous pressure and heart rate increased (p<0.05).”
Quote in the paperNot a substantial claim - Findingown data
During steady state AVP infusion, forearm blood flow rose from 3.4 ± 0.6 to 4.1 ± 0.7 ml/min/dl (p<0.05).
“Forearm blood flow rose from 3.4 ±0.6 ml/min/dl in control to 4.1 ±0.7 ml/min/dl during AVP infusion (p<0.05)”
Quote in the paperSubstantial claim - Findingown data
During steady state AVP infusion, central venous pressure increased from 3.1 ± 0.5 to 4.1 ± 0.8 mm Hg (p<0.05).
“there were increases in both central venous pressure (from 3.1 ±0.5 to 4.1 ±0.8 mm Hg; p<0.05)”
Quote in the paperNot a substantial claim - Findingown data
During the initial 10 minutes of AVP infusion, heart rate displayed a biphasic response, falling initially and then tending to increase toward the end of this period.
“Heart rate displayed a biphasic response, falling initially and then tending to increase toward the end of this period.”
Quote in the paperNot a substantial claim - Findingcitation
This dose of AVP (4 ng/kg/min) increased plasma AVP concentrations well beyond the normal physiological range.
“This dose of AVP (4 ng/kg/min) increased plasma AVP concentrations well beyond the normal physiological range.30”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] 30. Cowley AW. Vasopressin and cardiovascular regulation. Int Rev Physiol 1982;26:189-242
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingown data
At 15 minutes of AVP infusion (n=12), forearm vascular resistance fell (p<0.05).
“forearm vascular resistance fell (p<0.05)”
Quote in the paperSubstantial claim - Findingown data
During steady state AVP infusion, forearm vascular resistance fell from 34 ± 5 to 29 ± 5 resistance units (p<0.05).
“forearm vascular resistance fell from 34 ± 5 to 29 ± 5 resistance units (/?<0.05”
Quote in the paperSubstantial claim - Findingown data
During the first 5 minutes of AVP infusion (n=8), integrated sympathetic nerve activity decreased from 271 ± 45 to 156 ± 33 units (p<0.05).
“integrated sympathetic nerve activity decreased from 271 ± 45 to 156 ± 33 units (p<0.05).”
Quote in the paperSubstantial claim - Findingown data
Sympathetic nerve activity remained below control levels throughout the AVP infusion (202 ± 31 vs 254 ± 40 units before infusion; p<0.05).
“Sympathetic nerve activity remained below control levels throughout the infusion (202 ± 31 vs 254 ± 40 units before infusion; p<0.05).”
Quote in the paperSubstantial claim - Findingown data
The sympathoexcitatory response to apnea was not attenuated during AVP infusion.
“the sympathoexcitatory response to apnea was not attenuated during vasopressin.”
- Also stated in: § Effect of Apnea · plain
“reflex sympathoneural excitation was not altered by AVP even though resting nerve discharge was significantly attenuated at this time.”
Quote in the paperSubstantial claim - Also stated in: § Effect of Apnea · plain
- Findingown data
During the initial 10 minutes of AVP infusion, central venous pressure was not altered.
“Central venous pressure was not altered.”
Quote in the paperNot a substantial claim - Findingown data
During the initial 10 minutes of AVP infusion, forearm blood flow did not change.
“Forearm blood flow did not change.”
Quote in the paperNot a substantial claim - Findingown data
At 15 minutes of AVP infusion (n=12), heart rate increased (p<0.05).
“central venous pressure and heart rate increased (p<0.05).”
Quote in the paperNot a substantial claim - Findingown data
During steady state AVP infusion, heart rate increased from 65 ± 3 to 72 ± 3 beats/min (p<0.05).
“heart rate (from 65 ± 3 to 72 ± 3 beats/ min; p< 0.05”
Quote in the paperNot a substantial claim - Findingown data
SNA fell significantly within the first 2 minutes of AVP infusion.
“SNA, expressed either in terms of bursts per minute or per 100 heartbeats, or in units of integrated SNA, fell significantly within the first 2 minutes of AVP”
Quote in the paperSubstantial claim - Findingown data
Systemic and forearm hemodynamics returned to control levels within 10 minutes after stopping the AVP infusion.
“Systemic and forearm hemodynamics returned to control levels within 10 minutes after stopping the AVP infusion.”
Quote in the paperNot a substantial claim - Interpretationown data
The dissociation of changes in heart rate and SNA suggests a selectively greater inhibition of SNA than of heart rate by AVP.
“The dissociation of changes in heart rate and SNA suggests a selectively greater inhibition of SNA than of heart rate by AVP.”
Quote in the paperSubstantial claim - Interpretationown data
AVP did not exert a major ganglionic blocking action.
“This finding suggests that AVP did not exert a major ganglionic blocking action.”
Quote in the paperSubstantial claim- Rests on an assumption: The sympathoexcitatory response to apnea is mediated by ganglionic transmission and would be attenuated by a ganglionic blocking action.
- Interpretationown data
Infusion of AVP, 4 ng/kg/min, inhibits efferent muscle SNA.
“In summary, we have shown that infusion of AVP, 4 ng/kg/min, inhibits efferent muscle SNA.”
Quote in the paperSubstantial claim - Interpretationreasoning
The sympathoinhibition may have resulted principally from mechanical stimulation of cardiac and arterial baroreceptors.
“The sympathoinhibition may have resulted principally from mechanical stimulation of cardiac and arterial baroreceptors.”
Quote in the paperSubstantial claim- Rests on an assumption: The measured increases in central venous pressure (averaging 1 mm Hg) and transient increases in arterial pressure are sufficient to stimulate arterial and cardiac baroreceptors and produce reflex sympathoinhibition.
- Premisecitation
A marked pressor effect of AVP is unmasked by sinoaortic denervation in dogs and other species.
“A marked pressor effect of AVP is unmasked by sinoaortic denervation in dogs and other species.3”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] 3. Cowley AW, Monos E, Guyton AC. Interaction of vasopressin and the baroreceptor reflex system in the regulation of arterial blood pressure in the dog. Circ Res 1974;34:505-514 source
- Interpretationreasoning
The lack of change in forearm vascular resistance during initial AVP infusion may be explained by the balance between the direct vasoconstrictor effect of AVP and reflex sympathoinhibition.
“The lack of change in forearm vascular resistance may be explained by the balance between the direct vasoconstrictor effect of AVP and reflex sympathoinhibition.”
Quote in the paperSubstantial claim - Interpretationown data
The sympathoinhibition may be caused in part by the modest increases in mean arterial and central venous pressures and attendant stimulation of arterial and cardiac baroreceptors.
“The sympathoinhibition may be caused in part by the modest increases in mean arterial and central venous pressures and attendant stimulation of arterial and cardiac baroreceptors.”
Quote in the paperSubstantial claim- Rests on an assumption: The measured increases in central venous pressure (averaging 1 mm Hg) and transient increases in arterial pressure are sufficient to stimulate arterial and cardiac baroreceptors and produce reflex sympathoinhibition.
- Interpretationown data
The decreases in SNA did not appear to result from ganglionic blockade.
“The decreases in SNA did not appear to result from ganglionic blockade.”
Quote in the paperSubstantial claim- Rests on an assumption: The sympathoexcitatory response to apnea is mediated by ganglionic transmission and would be attenuated by a ganglionic blocking action.
- Interpretationreasoning
Sympathoinhibition would appear to be an important mechanism by which the potent pressor effects of AVP are countered in normal humans with intact baroreceptor reflexes.
“Sympathoinhibition would appear to be an important mechanism by which the potent pressor effects of AVP are countered in normal humans with intact baroreceptor reflexes.”
Quote in the paperSubstantial claim
- May combine two claims. 12
- Classified as probably not a substantial claim. 4
May combine two claims.
Premiseown dataIn normal subjects, AVP infusion at 4 ng/kg/min increased central venous pressure but did not raise mean arterial pressure or pulse pressure.
“This response was accompanied by increases in central venous pressure, but mean arterial pressure and pulse pressure did not rise.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] 5. Aylward PE, Floras JS, Leimbach WN, Abboud FM. Effect of vasopressin on the circulation and its baroreflex control in normal humans. Circulation 1986;73:1145-1154 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationIdentification of sympathetic bursts by two independent observers had a mean intraobserver variability of 4.3% and a mean interobserver variability of 9.1%.
“Mark et al. 18 reported a mean intraobserver variability of 4.3% and a mean interobserver variability of 9.1%.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [18] 18. Mark AL, Victor RG, Nerhed C, Wallin BG. Microneuro- graphic studies of the mechanisms of sympathetic nerve re- sponses to static exercise in humans. Circ Res 1985;57. 461-469 source
May combine two claims.
Findingown dataDuring steady state AVP infusion, neither systolic, mean, nor diastolic arterial pressure was altered from control values.
“During the steady state period, neither systolic, mean, nor diastolic arterial pressure was altered from control values.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDuring steady state AVP infusion, SNA fell from 20.5 ± 2.8 to 17.3 ± 2.5 bursts/min, from 31.1 ± 3.9 to 23.8 ± 3.2 bursts/100 heartbeats, and from 254 ± 40 to 202 ± 31 units (integrated SNA).
“SNA fell from 20.5 ±2.8 to 17.3 ±2.5 bursts/min, from 31.1 ±3.9 to 23.8 ±3.2 bursts/100 heartbeats, and from 254 ± 40 to 202 ± 31 units (integrated SNA) during steady state infusion of AVP”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataDuring the initial 10 minutes of AVP infusion, forearm resistance tended to increase briefly, but this was not significant.
“Forearm resistance tended to increase briefly, but this was not significant.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSNA adjusted for heart rate remained low (23.2 ± 3.9 bursts/100 heartbeats) 10 minutes after AVP infusion was stopped and then returned to control levels.
“However, SNA adjusted for heart rate remained low (23.2 ± 3.9 bursts/100 heartbeats) 10 minutes after the AVP infusion was stopped”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn the present study, forearm vasodilation was observed during the steady state period of AVP infusion when SNA was reduced.
“In the present study, we again observed forearm vasodilation during the steady state period of the AVP infusion when SNA was reduced.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSNA expressed as bursts per minute or integrated SNA rose toward control levels and was not significantly different from control during recovery.
“SNA, expressed as bursts per minute or as integrated SNA, rose toward control levels and was not significantly different from control levels during recovery.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataPathophysiologic levels of vasopressin in humans cause inhibition of muscle sympathetic nerve activity that is not due to a ganglionic blocking action.
“Thus, pathophysiologic levels of vasopressin in humans cause inhibition of muscle sympathetic nerve activity that is not due to a ganglionic blocking action.”
Quote in the paperSubstantial claim- Rests on an assumption: The sympathoexcitatory response to apnea is mediated by ganglionic transmission and would be attenuated by a ganglionic blocking action.
May combine two claims.
Interpretationown dataDuring steady state AVP infusion, forearm vasodilation may be explained by sustained inhibition of SNA, which appears to override the direct constrictor effect of AVP in the forearm.
“The forearm vasodilation may be explained by the sustained inhibition of SNA, which appears to override the direct constrictor effect of AVP in the forearm.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductcitationStable microneurographic recordings can be maintained and are not affected by time or infusion of vehicle.
“Stable recordings can be maintained with the microneurographic technique and are not affected by time or infusion of vehicle.20”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] 20. Leimbach WN, Kempf J, Mark AL. Intraneural recordings of sympathetic nerve activity in humans before and after lidocaine [Abstract]. Clin Res 1986;33:8HA
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
InterpretationreasoningThe reflex decrease in sympathetic nerve activity would be expected to buffer the direct vasoconstrictor effects of vasopressin.
“The reflex decrease in sympathetic nerve activity would be expected to buffer the direct vasoconstrictor effects of vasopressin.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Interpretationown dataSince the reduction in SNA was not consistently associated with detectable increases in arterial pressure or central venous pressure, the possibility that AVP decreased SNA in part by sensitizing baroreceptor afferents or by a central neural action cannot be excluded.
“However, since the reduction in SNA was not consistently associated with detectable increases in arterial pressure or central venous pressure, we cannot exclude the possibility that AVP decreased SNA in part by sensitizing baroreceptor afferents 12 -l5 or by a central neural action.8 - 12”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [12] 12. Guo GB, Schmid PG, Abboud FM. Sites at which vasopressin facilitates the arterial baroreflex in rabbits. Am J Physiol 1986;251:H644-H655
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [15] 15. Abboud FM, Aylward PE, Floras JS, Gupta BN. Sensitization of aortic and cardiac receptors by arginine vasopressin in mam- mals. J Physiol (Lond) 1986;377:251-265 source
- cites [8] 8. Liard J-F, Deriaz O, Tschopp M, Schoun J. Cardiovascular effects of vasopressin infused into the vertebral circulation of conscious dogs. Clin Sci 1981;61:345-347 source
The paper relies on this without support.
The sympathoexcitatory response to apnea is mediated by ganglionic transmission and would be attenuated by a ganglionic blocking action.
“This stimulus increased sympathetic discharge and served 1) to determine the stability of the recording site throughout the experiment at times when basal activity was suppressed and 2) to determine whether AVP might inhibit efferent sympathetic activity through a ganglionic blocking action.”
“An effect of vasopressin on ganglionic transmission was excluded, since the sympathoexcitatory response to apnea was not attenuated during vasopressin.”
The paper relies on this without support.
The measured increases in central venous pressure (averaging 1 mm Hg) and transient increases in arterial pressure are sufficient to stimulate arterial and cardiac baroreceptors and produce reflex sympathoinhibition.
“The sympathoinhibition we observed could be attributed to stimulation of arterial or cardiopulmonary receptors by these changes, resulting in a reflex withdrawal of efferent SNA.”
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Self-citationEffects of OPC-21268, an orally effective vasopressin V1 receptor antagonist in humans.
Imaizumi, T., Harada, S., Hirooka, Y., et al. (1992) · Hypertension · doi:10.1161/01.hyp.20.1.54 · Cited by 26 · see citing works
Platelet vasopressin receptors in patients with congenital nephrogenic diabetes insipidus
Bichet, D. G., Arthus, M., & Lonergan, M. (1991) · Kidney International · doi:10.1038/ki.1991.83 · Cited by 26 · see citing works
Attenuated cardiac baroreflex in men with presyncope evoked by lower body negative pressure
Wijeysundera, D. N., Butler, G. C., Ando, S., Pollard, M. J., Picton, P. E., & Floras, J. S. (2001) · Clinical Science · doi:10.1042/cs1000303 · Cited by 21 · see citing works
Self-citationHuman Sympathetic Nerve Activity and Blood Pressure Regulation
Wallin, B. G. (1989) · Clinical and Experimental Hypertension · doi:10.3109/10641968909045415 · Cited by 16 · see citing works
Neurohormonal Profile Before and After β‐Blockade in Patients with Neurocardiogenic Syncope
Roul, G., RIEHL‐ALEIL, V., Germain, P., & Bareiss, P. (1999) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.1999.tb00566.x · Cited by 14 · see citing works
Rongen, G. A. P. J. M., Senn, B. L., Ando, S., Notarius, D. F., Stone, J. A., & Floras, J. S. (1997) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y97-005 · Cited by 14 · see citing works
“Postganglionic multifiber SNA was recorded from a muscle fascicle of the right peroneal nerve posterior to the fibular head, using a microneurographic technique (Delius et al. 1972; Floras et al. 1987).”
MethodSelf-citationRothman, J. L. S., Easty, A., Frecker, R. C., & Floras, J. S. (1991) · Computers in Biology and Medicine · doi:10.1016/0010-4825(91)90004-s · Cited by 13 · see citing works
Self-citationHeusser, K., Wittköpper, J., Bara, C., Haverich, A., Diedrich, A., Levine, B. D., Schmitto, J. D., Jordan, J., & Tank, J. (2021) · European Journal of Heart Failure · doi:10.1002/ejhf.2344 · Cited by 9 · see citing works
Hormonal Modulation of Baroreceptor Reflexes
BISHOP, V. S., Shade, R. E., & Haywood, J. R. (1991) · doi:10.1007/978-3-642-76366-3_9 · Cited by 6 · see citing works
Muratani, H., Kimura, Y., Matsumura, K., Noda, Y., Eto, T., & Fukiyama, K. (1990) · Clinical and Experimental Hypertension · doi:10.3109/10641969009074722 · Cited by 6 · see citing works
Hemodynamic Response to Vasopressin in Dehydrated Human Subjects
Huch, K. M., Wall, B. P., Mangold, T. A., et al. (1998) · Journal of Investigative Medicine · doi:10.1177/170882679804600612 · Cited by 4 · see citing works
Madkour, L. H., Bedoya, L. A., & Fouad-Tarazi, F. M. (1992) · Clinical Autonomic Research · doi:10.1007/bf01819545
- Authors
- Floras, J. S., Aylward, P. E., Abboud, F. M., & Mark, A. L.
- Affiliations
- University of Iowa (US)
- Venue
- Hypertension
- Published
- 1987-10
- Volume
- 10
- Issue
- 4
- Pages
- 409-416
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2153984547
- Cited by
- 21
- References
- 31
- Citations by year
- 2021: 1 · 2017: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart Foundation of Australia
- National Institutes of Health (14388, HL14388)
- National Heart, Lung, and Blood Institute (HL-24962, HL-14388)
- National Center for Research Resources
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- vasopressin, muscle sympathetic nerve activity, baroreflex, vasoconstriction, arterial pressure, forearm vascular resistance, central venous pressure, heart rate, apnea, ganglionic transmission, peroneal nerve
- MeSH terms
- Adult, Arginine Vasopressin, Humans, Male, Muscles, Pressoreceptors, Reflex, Sympathetic Nervous System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.
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