Venous Versus Arterial Forearm Catecholamines as an Index of Overall Sympatho-Adrenomedullary Activity

The metabolism of norepinephrine (NE) and epinephrine (EPI) in peripheral tissues limits the use of venous plasma levels of these parameters as an index of overall sympathetic or adreno-medullary activity. Therefore venous (deep antecubital vein) and arterial (brachial artery) concentrations of NE and EPI were compared in 16 hypertensive subjects. NE and EPI were determined after 30 min supine rest, and immediately before and after isometric exerise, cold provocation, head-up tilting (OST) and Stroop's colour word test (CWT). At rest venous NE exceeds arterial NE. Assuming similar fractional extractions (FE) of NE and EPI, 46±14% (mean±SD) of venous NE appeared to be produced locally. Despite this considerable local production venous and arterial levels of NE were closely correlated (r=0.92). At rest venous EPI was 42±13% lower than arterial EPI, but since the interindividual variation of the FE of EPI was relatively small and independent of arterial levels, venous and arterial levels were also closely correlated (r=0.82). All four tests caused an increase in arterial and venous NE, whereas EPI did not change. Responses of arterial and venous NE were only correlated after OST and CWT. It is concluded that at rest, but not invariably so during different forms of sympatho-adrenal activation, arterial plasma concentrations of NE and EPI can be substituted for by their respective venous equivalents. Clinical and Experimental Hypertension, Volume 11, Issue S1 1989 , pages 345 - 351

Antibody responses

Chemical sympathectomy of peripheral nerves has been demonstrated to augment antibody response following immunization with specific antigen.

Surgery: Basic Science and Clinical Evidence

By Jeffrey A. Norton, R. Randall Bollinger

Contributor Jeffrey A. Norton

Edition: illustrated

Published by Springer, 2001

ISBN 038798447X, 9780387984476

Norepinephrine response to mental challenge

DS Goldstein, G Eisenhofer, FL Sax, HR Keiser and IJ Kopin
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.

We simultaneously infused tracer-labeled norepinephrine (NE) and isoproterenol (ISO) intravenously into 14 subjects to measure forearm and total body NE pharmacokinetics at rest and in response to mental challenge (video game or cognitive task). Mental challenge was associated with significantly increased heart rate (24%), systolic blood pressure (13%), cardiac output (impedance cardiography, 9%), forearm blood flow (38%), and the rate of release of endogenous NE into arterial blood (total body NE spillover, 29%), but not with changes in cardiac output (r = 0.68) and systolic blood pressure (r = 0.60), whereas those of antecubital venous NE were not. Forearm extraction of NE was related inversely to forearm blood flow both at rest (r = -0.80) and during mental challenge (r = -0.81), and total body clearance of NE was positively related to cardiac output at rest (r = 0.78) and during mental challenge (r = 0.54). The results indicate that mental challenge is associated with generally increased sympathetically-mediated NE release that determines the hemodynamic responses. Because of regional changes in sympathetic activity and blood flow during psychological stress, changes in antecubital venous NE and even arterial NE may not reflect accurately sympathetic nerve activity. Measurement of total body and regional NE pharmacokinetics avoids these difficulties.
Psychosomatic Medicine, Vol 49, Issue 6 591-605, Copyright © 1987 by American Psychosomatic Society

The integrative relationship between insulin and insulin-like growth factor 1-induced cardiovascular responses and sympathetic nervous responses

Lumbar sympathectomy caused greater increase in skeletal muscle blood flow in response to both insulin and IGF-1 when hypoglycemia occurred. But when hypoglycemia was prevented, IGF-1 induced increase in blood flow was suppressed in sympathetic denervated iliac artery. We concluded that insulin and IGF-1 have both similar and distinct effects on cardiovascular system and sympathetic nervous system. They both may act directly on vasculature to elicit vasodilation thus decrease MAP Insulin can selectively increase sympathetic nerve activity, while IGF-1 decreases sympathetic nerve activity.
Zhengbo Duanmu, Wayne State University

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished

Vasoconstrictor responses to immersion of the hand in ice water in the sympathetically denervated forearm were abolished; during the second minute of the cold pressor test, vascular resistance had increased by 48±20 percent in the innervated limb, whereas it had decreased by 17±5 percent in the denervated limb (P<0.02> limbs).

Figs. 1 and 2 show that L-NMMA infusion evoked a roughly 3-fold larger increase in vascular resistance in the denervated forearm than in the innervated calf. In the forearm, vascular resistance increased by 58±10 percent during L-NMMA infusion whereas in the calf, it increased only by 21±6 percent (P<0.001, forearm vs. calf). The L-NMMA induced vasoconstriction was reversed by L-arginine, but not by D-arginine, infusion (Table 1). In contrast to L-NMMA, infusion of an equipressive dose of phenylephrine increased the vascular resistance comparably in the denervated and the innervated limb (by 24±3 and 26±7 percent, respectively; P>0.5, forearm vs. calf).

Here we used subjects having undergone thoracic sympathectomy for hyperhydrosis, to probe the role of the peripheral sympathetic nervous system in the modulation of the vascular responsiveness to nitric oxide synthase inhibition. We found that sympathectomy markedly potentiated the vasoconstrictor effect of L-NMMA infusion. The L-NMMA induced vasoconstrictor effect was almost three times larger in the denervated than in the innervated limb. These findings provide the first evidence for an important interplay between the peripheral sympathetic nervous system and the L-arginine–nitric-oxide system in the regulation of the vascular tone in humans, and indicate that sympathetic innervation attenuates the vasoconstrictor effect of nitric oxide synthase inhibition.

Cardiovascular Research 1999 43(3):739-743; doi:10.1016/S0008-6363(99)00084-X
© 1999 by European Society of Cardiology

Effect of autonomic and adrenal manipulation on the serum insulin level

3. Journal of Tissue Research Vol. 4 (1) 83-88 (2004) Pilo, B. and Yadav, V.

Division of Neuroendocrinology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara-390 002 India. Email: bonnypilo@satyam.net.in

Mammalian glucose homoeostasis is partially controlled by glucose sensor mechanisms in the pancreatic endocrine cells and partially through autonomic nerves. The influence of the autonomic nervous system on pancreatic insulin secretion has been studied in the present study. Vagal sectioning decreased serum insulin significantly compared to that of the sham operated rats which could be the reason for the resulting hyperglycaemic condition prevailed in these rats. Bilateral adrenalectomy and chemical sympathectomy singly increased insulin level to the same extent. Even, when vagotomy was performed together with adrenalectomy, insulin level declined but this decrease is not as significant as that in vagotomized rats. Similar result was obtained with rat treated for chemical sympathectomy and vagotomy together and this slight decrease in insulin level could favour marginal hyperglycaemia.

Insulin receptors

Glucose metabolism, however, was inhibited by chemical sympathectomy: the glucose transport rate was significantly reduced and fatty acid synthesis was nearly totally abolished. Insulin was still effective in stimulating both parameters but failed to restore normal levels. The results suggest that the sympathetic innervation of adipose tissue may exert an inhibitory effect on the number of high-affinity insulin receptors as well as on the sensitivity of the lipolysis to insulin, as both parameters were increased by sympathectomy. To explain the inhibitory effect of 6-hydroxydopamine treatment on glucose transport and fatty acid synthesis, a possible trophic effect of the sympathetic innervation is discussed as well as indirect mechanism counteracting the effects of the chemical sympathectomy.

Effects of chemical sympathectomy on insulin receptors and insulin action in isolated rat adipocytes

HG Joost and SH Quentin

Volume 229, Issue 3, pp. 839-844, 06/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

incomplete sympatholysis achieved by thoracoscopic sympathicotomy

Skin temperature variations did not correlate to skin perfusion changes. Since all subjects reported dry and warm hands throughout the follow-up period, our results indicate that recording reflex responses to sympathoexcitatory stimuli does not adequately reflect clinical outcome of subtotal sympatholytic procedures performed for hyperhidrosis. Monitoring of clinical outcome should therefore include measurement of baseline sweat production and skin perfusion. However, the normalized reflex responses highlight the incomplete sympatholysis achieved by thoracoscopic sympathicotomy, which may be beneficial in some pathological conditions (such as hyperhidrosis) but detrimental in others. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1486-1492, 1998

---

Received: 2 November 1997; Accepted: 14 April 1998

Muscle & Nerve

Volume 21 Issue 11, Pages 1486 - 1492

Published Online: 7 Dec 1998

Copyright © 2009 Wiley Periodicals, Inc., A Wiley Company

Reflex sympathetic dystrophy syndrome and neuromediators

Concepts related to the pathophysiology of reflex sympathetic dystrophy syndrome (RSDS) are changing. Although sympathetic influences are still viewed as the most likely mechanism underlying the development and/or perpetuation of RSDS, these influences are no longer ascribed to an increase in sympathetic tone. Rather, the most likely mechanism may be increased sensitivity to catecholamines due to sympathetic denervation with an increase in the number and/or sensitivity of peripheral axonal adrenoceptors. Several other pathophysiological mechanisms have been suggested, including neurogenic inflammation with the release of neuropeptides by primary nociceptive afferents and sympathetic efferents. These neuromediators, particularly substance P, calcitonin gene-related peptide, and neuropeptide Y (NPY), may play a pivotal role in the genesis of pain in RSDS.

Thao Pham^, and Pierre Lafforgue
Joint Bone Spine
Volume 70, Issue 1, 1 February 2003, Pages 12-17

significantly more cholesterol and total lipids in the aorta after sympathectomy

While the vasomotor effect of the sympathetic nervous system (SNS) on the arterial wall is well recognized, its trophic function is not. It is the aim of these studies to demonstrate this all-important function as it relates to the vascular muscle.

Although the exact mechanism by which sympathetic nerve impulses influence the metabolism of the vessel wall is unknown, effects of sympathectomy can be demonstrated. Several lines of evidence indicate that chronic absence of sympathetic innervation in rabbits increases collagen synthesis and decreases activity of tricarboxylic acid cycle enzymes in the vascular wall. When chemically sympathectomized rabbits were fed a 1% cholesterol dietary supplement for 80 days, the aortas of these rabbits contained significantly more cholesterol and total lipids than those from fully innervated controls in spite of insignificant differences in plasma lipids.

In a subsequent series of experiments we analyzed the efficacy of the SNS in two strains of pigeons. White Carneau (WC) pigeons are known by their susceptibility to atherosclerosis of the aorta while Show Racer (SR) pigeons are not. Our results demonstrate that the abdominal aorta of WC pigeons has less sympathetic innervation and it declines faster with age than that of SR pigeons. The results of the described studies documenting the direct trophic influence of the SNS on the arterial wall are reinforced by the similarity to the vessel wall changes induced by partial sympathectomy and natural aging.

Trophic effect of the sympathetic nervous system on vascular smooth muscle

	Annals of Biomedical Engineering
	Springer Netherlands
ISSN	0090-6964 (Print) 1573-9686 (Online)
Issue	Volume 11, Number 6 / November, 1983

Partial cardiac sympathetic denervation after bilateral thoracic sympathectomy in humans

Partial cardiac sympathetic denervation after bilateral thoracic sympathectomy in humans
Heart Rhythm, Volume 2, Issue 6, Pages 602-609
J.Moak, B.Eldadah, C.Holmes, S.Pechnik, D.Goldstein

All four patients with bilateral sympathectomy had low septal myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity (2,673 ± 92 nCi-kg/cc-mCi at an average of 89 minutes after injection) compared with normal volunteers (3,634 ± 311 nCi-kg/cc-mCi at 83 minutes, N = 22, P = .007) and higher radioactivity than in patients with pure autonomic failure (1,320 ± 300 nCi-kg/cc-mCi at 83 minutes, N = 7, P = .003). Patients with unilateral sympathectomy had normal 6-[¹⁸F]fluorodopamine-derived radioactivity (3,971 ± 337 nCi-kg/cc-mCi at 87 minutes).

Conclusions

Bilateral upper thoracic sympathectomy partly decreases cardiac sympathetic innervation density.

spontaneous flow oscillations occurred in the sympathectomized limbs

We measured arterial and venous plasma catecholamines and used laser-Doppler flowmetry to measure cutaneous microcirculatory flow in the sympathectomized and in the intact limbs of 3 patients who had undergone regional sympathectomies. Venous concentrations of norepinephrine, the sympathetic neurotransmitter, exceeded arterial concentrations in the intact limbs--a normal finding--but invariably were less than arterial in the sympathectomized limbs of the same patients, both during baseline conditions and during sympathetic stimulation using tilt, standing and the cold pressor test (mean arteriovenous decrement about 40%). Arterial epinephrine levels exceeded venous levels with or without sympathectomy. Skin microvascular flow rapidly decreased during the cold pressor test and the Valsalva maneuver in the intact but not in the sympathectomized limbs, and spontaneous flow oscillations occurred in the sympathectomized limbs. The results suggest that an arteriovenous increment in plasma norepinephrine reflects local release of norepinephrine from sympathetic nerve endings, whereas removal of circulating catecholamines can occur with or without sympathetic neural impulses. Laser-Doppler flowmetry can measure reflexive sympathetically mediated responses of skin microvascular flow and so can detect sympathetic denervation. Spontaneous oscillations in this flow may not depend exclusively on oscillations in the activity of the sympathetic microvascular innervation.
J Auton Nerv Syst. 1986 Apr;15(4):309-18.
http://www.ncbi.nlm.nih.gov/pubmed/3517118

Unilateral and bilateral sympathectomy produced similar reductions in the concentrations of NPY-ir and NA in the ventricular tissue

Differential effects of surgical sympathectomy on rat heart concentrations of neuropeptide Y-immunoreactivity and noradrenaline.

Maccarrone C, Jarrott B.

University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Vic., Australia.
J Auton Nerv Syst. 1987 Dec;21(2-3):101-7
The aim of this study was to estimate the proportion of cardiac neuropeptide Y-immunoreactivity (NPY-ir) which is not present in sympathetic neurones innervating the rat heart. The procedure employed was to surgically sympathectomize the heart and then measure the remaining cardiac concentrations of NPY-ir and noradrenaline (NA). Unilateral (left) sympathectomy significantly reduced the levels of NPY-ir and NA in all regions of the heart (by 40-70%) except for the NPY-ir in the right atrium which was unaltered. The effect of bilateral sympathectomy was significantly greater than that of unilateral sympathectomy. Unilateral and bilateral sympathectomy produced similar reductions in the concentrations of NPY-ir and NA in the ventricular tissue. In contrast dissimilar changes were produced in the atrium. Although bilateral sympathectomy almost totally depleted the NA from the right atrium (by 98%), the NPY-ir levels were only reduced by 50%. These results indicate that approximately half the content of NPY in the right atrium is not present in sympathetic noradrenergic neurones. This pool may occur in the previously described intrinsic neurones of the right atrium.
PMID: 3450689 [PubMed - indexed for MEDLINE]