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(Hypertension. 1995;25:560-563.)
© 1995 American Heart Association, Inc.

Articles

Sympathetic Activation in Obese Normotensive Subjects

Guido Grassi; Gino Seravalle; Bianca M. Cattaneo; Giovanni B. Bolla; Antonio Lanfranchi; Manuela Colombo; Cristina Giannattasio; Amelia Brunani; Francesco Cavagnini; Giuseppe Mancia

From the Cattedra di Medicina Interna (G.G., M.C., C.G., G.M.) and Istituto di Clinica Medica (G.G., G.S., B.M.C., G.B.B., A.L.), Università di Milano, Ospedale S. Gerardo, Monza, and Ospedale Maggiore, Milano; Cattedra di Endocrinologia, Centro Auxologico Italiano (A.B., F.C.), Milano, Italy.

Correspondence to Prof Giuseppe Mancia, Centro Fisiologia Clinica e Ipertensione Via F. Sforza 35, 20122 Milano, Italy.

	Abstract

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Abstract Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5±1.2 kg/m², mean±SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6±5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7±1.3 bursts per minute), the difference being highly statistically significant (P<.02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.

Key Words: obesity • autonomic nervous system

	Introduction

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A major controversy exists as to whether obesity is characterized by adrenergic activation. In animals, increasing caloric intake was found to raise norepinephrine turnover.^{1 2} However, body weight was only modestly increased and no increase in norepinephrine secretion was reported in Zucker rats, ie, in a classic animal model of obesity.^{3 4 5} Furthermore, studies in obese normotensive men have reported an increase but also no change or even a reduction in plasma norepinephrine compared with the values in lean control subjects.^{6 7 8 9 10}

Plasma norepinephrine is an indirect and rather insensitive index of sympathetic activity because most of the norepinephrine secreted from the sympathetic fibers is destroyed or reuptaken, and only a minute fraction escapes from the neuroeffector junctions.^{11 12 13} However, this limitation can be overcome by the microneurographic technique that allows direct, precise, and reproducible measurement of sympathetic neural discharge from the human peroneal or brachial nerves.^{14 15} Microneurographic data have so far shown that, in some races, sympathetic nerve traffic may be related to body fat.¹⁶

In the present study we used the microneurographic technique to determine whether, at a young age and in the absence of any confounding effect of a blood pressure elevation,¹⁷ muscle sympathetic nerve activity (MSNA) is modified by obesity. In addition, we measured basal MSNA along with sympathetic responses to alterations in baroreceptor drive to determine whether the possible modification in sympathetic activity has a reflex nature.

	Methods

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Subjects
Subjects were 10 young males with markedly high body weight and body mass index. Eight lean males of a similar age served as control subjects (Table 1). Obese and lean subjects were recruited by the medical staff of the Centro Auxologico Italiano, where they were hospitalized for at least 1 week for the purpose of the study. As inpatients they consumed a weight-maintaining isocaloric diet containing 50% carbohydrate, 18% protein, 32% fat, and 217 mmol/24 h sodium. The level of physical activity, although not strictly standardized, was similar in obese and lean subjects, being restricted because of hospitalization. All subjects were normotensive (arterial blood pressure <140/85 mm Hg on repeated sphygmomanometric measurements) and had no family history of hypertension, alcohol consumption, or cigarette smoking. They were not taking any medication at the time of the study, and no cardiovascular disease or medical illness was observed at the routine medical and laboratory examinations performed in our outpatient clinic.

View this table: [in this window] [in a new window]   Table 1. Baseline Data

The study protocol was approved by the ethics committee of our institution, and the procedures performed were in accordance with institutional guidelines. The subjects agreed to participate and gave consent to the study after being informed of the nature and purpose of the study.

Measurements
Blood Pressure, Heart Rate, and Respiration Rate
Blood pressure was initially measured three times with a mercury sphygmomanometer, taking the first and fifth Korotkoff sounds to identify systolic and diastolic values and using a standard cuff and a thigh cuff (bladder, 150x330 mm or 150x360 mm) in control and obese subjects, respectively. In addition, arterial blood pressure was monitored in all subjects by a finger photoplethysmographic device (Finapres 2300, Ohmeda) capable of providing accurate and reproducible beat-to-beat systolic and diastolic values.^{18 19} Heart rate was continuously monitored by a cardiotachometer triggered by the R wave of an electrocardiographic lead. Respiration rate was monitored by a strain-gauge pneumograph positioned at the midchest level.

Sympathetic Nerve Traffic
Multiunit recording of efferent postganglionic MSNA was obtained from a microelectrode inserted in the right or left peroneal nerve posterior to the fibular head, as previously described.^{14 15} The microelectrode was made of tungsten and had a diameter of 200 µm in the shaft, tapering to 1 to 5 µm at the level of the uninsulated tip. A reference electrode positioned subcutaneously 10 to 30 mm from the recording electrode served as the ground. The nerve signal was amplified x70 000, fed through a band-pass filter (700 to 2000 Hz), and integrated with a custom nerve traffic analysis system (Bioengineering Department, University of Iowa, Iowa City). Integrated nerve activity was monitored by a loudspeaker, displayed on a storage oscilloscope (model 511A, Tektronix), and recorded with blood pressure, heart rate, and respiratory movements on an ink polygraph. The muscle nature of the MSNA was assessed according to the criteria outlined in previous studies,^{14 15} and the recording was accepted only if the signal-to-noise ratio was greater than 3.

Under baseline resting conditions, MSNA was quantified as bursts per minute and bursts per 100 heartbeats. Changes in MSNA during baroreceptor stimulation, baroreceptor deactivation, and the cold pressor test (see below) were quantified as absolute and percent changes of integrated MSNA (bursts per minute times mean burst amplitude, expressed in arbitrary units). Quantification of MSNA by this integration has been shown to be highly reproducible, ie, to differ by only 5% when assessed on the same tracing on two occasions by a single investigator.¹⁵

Plasma Norepinephrine and Plasma Renin Activity
Plasma norepinephrine was assayed the same day of the study by high-performance liquid chromatography²⁰ on a blood sample withdrawn from a cannula placed in an antecubital vein of the arm contralateral to that used for blood pressure measurements. Plasma renin activity was assayed by radioimmunoassay²¹ on blood withdrawn from the same cannula.

Baroreflex Evaluation and Cold Pressor Test
Baroreceptor modulation of MSNA and heart rate was assessed by a technique based on infusion of vasoactive drugs.²² Briefly, phenylephrine was incrementally infused in an antecubital vein at doses of 0.3, 0.6, and 0.9 mcg/kg per minute, each step being maintained for 5 minutes. Nitroprusside was also incrementally infused in an antecubital vein at doses of 0.4, 0.8, and 1.2 mcg/kg per minute, each step being maintained for 5 minutes. In both obese and lean subjects, the drug initially infused was randomly selected, and the end of the first infusion was separated from the beginning of the second by a recovery time of 45 minutes. Mean arterial pressure (diastolic pressure plus one third of pulse pressure), MSNA, and heart rate were averaged for the 5 minutes before infusion and for the 5 minutes of each step infusion. Baroreceptor modulation of MSNA and heart rate was estimated by calculating the absolute change in MSNA, the percent change in MSNA, and the absolute change in heart rate in relation to the change in mean arterial pressure induced by each dose of phenylephrine and nitroprusside. The changes in reflex heart rate and MSNA (percent values) in response to mean arterial pressure changes were also averaged separately for the three doses of phenylephrine and nitroprusside to obtain average baroreflex sensitivities during baroreceptor stimulation and deactivation of normalized stimuli.

Blood pressure, heart rate, and MSNA responses to the cold pressor test were evaluated 45 minutes after the end of the vasoactive drug infusion. The test was performed by immersion of the hand opposite the arm used for blood pressure measurements in iced water (3°C) for 2 minutes. Hemodynamic variables and MSNA were averaged for the 5 minutes before the cold pressor test and for the 2 minutes of the test.

Protocol and Data Analysis
Obese and lean subjects were taken to the laboratory in the morning after a light breakfast. All subjects were fitted with the intravenous cannula, the microelectrodes for MSNA recording, and the other measuring devices, and measurements were taken with the subjects in the supine position. Blood samples for assessment of plasma norepinephrine and plasma renin activity were taken, and blood pressure was measured three times with the mercury sphygmomanometer. After a 30-minute interval, blood pressure, heart rate, respiratory rate, and MSNA were continuously measured during (1) an initial 10-minute basal state, (2) infusion of one vasoactive drug, (3) a second 10-minute basal state, (4) infusion of the second vasoactive drug, (5) a 5-minute basal state, and (6) a 2-minute cold pressor test. A 45-minute recovery period was allowed before each 10-minute basal state.

Data were analyzed by a single investigator unaware of the experimental design. Baseline blood pressure, heart rate, and MSNA values from individual subjects were averaged for each group and expressed as mean±SEM. This was also done for the changes in mean arterial pressure, MSNA, and heart rate induced by each dose of phenylephrine or nitroprusside and by the cold pressor test. Comparisons between data from obese and lean subjects were made by two-way ANOVA. The Spearman analysis was used to determine the correlation between changes in different variables. Probability values of less than .05 were considered statistically significant.

	Results

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Basal Values
As shown in Table 1, blood pressure, heart rate, and breathing rate were similar in obese and control subjects. Blood pressure values were also similar in the two groups when they were measured beat-to-beat by the Finapres device, but plasma renin activity was significantly higher in obese subjects than in control subjects.

As shown in Fig 1, MSNA was about twice as high in obese subjects as in control subjects when expressed as either bursts per minute or bursts per 100 heartbeats. On the other hand, plasma norepinephrine was only slightly higher in obese subjects compared with control subjects, and the difference was not statistically significant (Fig 1). Plasma norepinephrine and MSNA were positively related in control subjects (r=.76, P<.05) but not in obese subjects (r=.35, P=NS), and not in obese and control subjects when their data were taken together (r=.44, P=NS). MSNA, but not plasma norepinephrine, was positively related to body mass index (r=.64, P<.01).

View larger version (10K): [in this window] [in a new window]   Figure 1. Bar graphs show muscle sympathetic nerve activity (MSNA, expressed as bursts per minute [bs/min] and bursts per 100 heartbeats [bs/100hb]) and plasma norepinephrine values (NE) in lean (open bars) and obese (hatched bars) subjects. Data are mean±SEM. **P<.02.

Baroreflex Data
As shown in Fig 2, infusion of the three incremental doses of phenylephrine caused a progressive increase in mean arterial pressure, a progressive decrease in heart rate, and a progressive reduction in MSNA, whereas infusion of the three incremental doses of nitroprusside had opposite effects. The changes in heart rate and MSNA induced by phenylephrine or nitroprusside were significantly smaller in obese subjects than in control subjects. The average baroreflex sensitivities during baroreceptor stimulation and deactivation were significantly reduced in obese subjects compared with lean subjects. The reduction was manifest for both heart rate and MSNA responses (Table 2).

View larger version (9K): [in this window] [in a new window]   Figure 2. Line graphs show changes in heart rate (HR, expressed in beats per minute [b/min]) and in muscle sympathetic nerve activity (MSNA, expressed in absolute, arbitrary units and as percent change) in response to changes in mean arterial pressure (MAP) by stepwise intravenous nitroprusside and phenylephrine infusions. Data are mean±SEM. *P<.05, **P<.02, lean (dashed lines) vs obese (continuous lines) subjects.

View this table: [in this window] [in a new window]   Table 2. Average Changes in Heart Rate and Muscle Sympathetic Nerve Activity in Response to Changes in Mean Arterial Pressure Induced by Phenylephrine or Nitroprusside

Cold Pressor Test
The cold pressor test induced similar increases in mean arterial pressure in control and obese subjects (13.5±2.3 versus 15.5±3.3 mm Hg, respectively) and heart rate (5.5±2.8 versus 4.5±1.2 beats per minute). MSNA increased during the cold pressor test, and the increase was similar in the two groups (71.6±8.7% versus 68.1±9.3%).

	Discussion

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The increase in sympathetic nerve traffic in our normotensive obese subjects was so pronounced that the postganglionic sympathetic nerve firing rate was twice that seen in lean control subjects. This provides direct, unequivocal evidence that human obesity is associated with a marked sympathetic activation and that this activation occurs in the absence of any blood pressure elevation.

Our results also show that the bradycardia and sympathoinhibition caused by baroreceptor stimulation were less in obese subjects than in control subjects and that this was also the case for the tachycardia and sympathoexcitation caused by baroreceptor deactivation. Thus, human obesity is associated with an impairment of the baroreceptor reflex that involves its cardiac and peripheral control. By reducing the afferent restraint on the vasomotor center, this impairment may be an important factor in the sympathetic activation of obesity. Because in obesity insulin sensitivity is reduced^{6 23} and, as shown by the present and other observations, plasma renin activity is increased,²⁴ another possible factor is an enhancement of sympathetic drive due to an increase in levels of circulating insulin, angiotensin II, or both.^{2 25}

Two other points are worthy of mention. The first is that the reasons for the baroreflex impairment associated with obesity are not clarified by our study. However, because the cardiovascular and sympathetic responses to the cold pressor test were similar in obese and control subjects, it is clear that the impairment is not part of a general dysfunction of autonomic cardiovascular modulation but rather represents a specific feature of the baroreflex. We can speculate that the baroreceptors themselves are involved because of a reduced distensibility of the arterial walls where these stretch receptors are located.²² The second point is that the marked increase in sympathetic nerve traffic in our obese subjects was not paralleled by a consistent increase in plasma norepinephrine concentration. Because plasma volume is increased in obesity,²⁶ the lack of an increase in plasma norepinephrine may be due to hemodilution. It may also be due to an increase in cardiac output and tissue blood flow.^{26 27 28} Another possibility is that sympathetic activation does not involve the entire circulation, the amount of norepinephrine secreted being too small to increase its concentration in the whole systemic reservoir. Whatever the mechanisms, however, our findings show that obesity may be a condition in which a sympathetic activation is less easily detectable by measurement of plasma norepinephrine level than by microneurography, which may therefore be a more sensitive sympathetic marker.

Our results have two pathophysiological implications. The first is that the marked sympathetic activation observed in obese normotensive subjects may be one of the factors facilitating, in the long term, the development of hypertension, a condition much more frequent in overweight than in lean people.^{29 30} The second is that the increased sympathetic activity and reduced vagal drive resulting from baroreflex impairment may account for the increased rate of arrhythmias and sudden death reported in obese people.³¹ Because of these implications, it will be important to determine whether the autonomic alterations associated with obesity are reversible by reduction in body weight.

Received March 11, 1994; first decision May 16, 1994; accepted November 11, 1994.

	References

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1. Young JB, Saville E, Rothweil NJ, Stock MJ, Landsberg L. Effect of diet and cold exposure on norepinephrine turnover in brown adipose tissue of the rat. J Clin Invest. 1982;69:1061-1071.
2. Landsberg L, Krieger DR. Obesity, metabolism, and the sympathetic nervous system. Am J Hypertens. 1989;2(suppl 2):125S-132S.
3. Levin BE, Triscari J, Sullivan AC. Defective catecholamine metabolism in peripheral organs in genetically obese Zucker rats. Brain Res. 1981;224:353-366. [Medline] [Order article via Infotrieve]
4. Knehans A, Romsos DR. Reduced norepinephrine turnover in brown adipose tissue of ob/ob mice. Am J Physiol. 1982;242:E253-E261. [Abstract/Free Full Text]
5. Levin BE, Triscari J, Sullivan AC. Studies of origins of abnormal sympathetic function in obese Zucker rats. Am J Physiol. 1983;245:E87-E93. [Abstract/Free Full Text]
6. Sowers JR, Whitfield LA, Catania RA, Stern R, Tuck ML, Dornfeld LP, Maxwell M. Role of the sympathetic nervous system in blood pressure maintenance in obesity. J Clin Endocrinol Metab. 1982;54:1181-1187. [Abstract]
7. Reisin E, Frohlich ED, Messerli FA, Dreslinski GR, Gunn FG, Jones MM, Batson HM Jr. Cardiovascular changes after weight reduction in obesity hypertension. Ann Intern Med. 1983;98:315-319.
8. De Haven J, Sherwin R, Handler R, Felig P. Nitrogen and sodium balance and sympathetic nervous system activity in obese subjects treated with a low-caloric protein or mixed diet. N Engl J Med. 1980;302:477-482. [Abstract]
9. Peterson HR, Rothschild M, Weinberg CR, Fell RD, Macleish KR, Pfeifer MA. Body fat and the activity of the autonomic nervous system. N Engl J Med. 1988;318:1077-1083. [Abstract]
10. Jung RT, Shetty PS, James WPT, Barrand MA, Callingham BA. Reduced thermogenesis in obesity. Nature. 1979;279:322-323. [Medline] [Order article via Infotrieve]
11. Folkow B, Di Bona FG, Hjemdahl P, Toren HP, Wallin BG. Measurements of plasma noradrenaline concentrations: a word of caution. Hypertension. 1983;5:399-403. [Abstract/Free Full Text]
12. Esler MD, Hasking GJ, Willett IR, Leonard PN, Jennings GL. Noradrenaline release and sympathetic nervous system activity. J Hypertens. 1985;3:117-129. [Medline] [Order article via Infotrieve]
13. Mancia G, Grassi G, Parati G, Daffonchio A. Evaluating sympathetic activity in human hypertension. J Hypertens. 1993;11(suppl 5):S13-S19.
14. Vallbo AB, Hagbarth KE, Torebjork HE, Wallin BG. Somatosensory, proprioceptive and sympathetic activity from peripheral nerves. Physiol Rev. 1979;59:919-957. [Free Full Text]
15. Mark AL, Victor RH, Nerhed C, Wallin BG. Microneurographic studies of the mechanisms of sympathetic nerve responses to static exercise in humans. Circ Res. 1985;57:461-469.[Abstract/Free Full Text]
16. Spraul M, Ravussin E, Fontvieille AM, Rising R, Larson DE, Anderson EA. Reduced sympathetic nervous activity: a potential mechanism predisposing to body weight gain. J Clin Invest. 1993;92:1730-1735.
17. Andersson B, Wallin G, Hedner T, Ahlberg AC, Andersson OK. Acute effects of short-term fasting on blood pressure, circulating noradrenaline and efferent sympathetic nerve activity. Acta Med Scand. 1988;223:485-490. [Medline] [Order article via Infotrieve]
18. Wesserling KH, De Witt B, Settles JJ, Klaver WH. On the indirect registration of finger blood pressure after Penaz. Funct Biol Med. 1982;1:245-250.
19. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension. 1989;13:647-655. [Abstract/Free Full Text]
20. Hijemdal P, Daleskog M, Kanan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979;25:131-138. [Medline] [Order article via Infotrieve]
21. Sealey JE, Laragh JH. How to do a plasma renin assay. Cardiovasc Med. 1977;2:1079-1092.
22. Mancia G, Mark AL. Arterial baroreflex in humans. In: Shepherd JT, Abboud FM, eds. Handbook of Physiology, Section 2: The Cardiovascular System. Bethesda, Md: American Physiological Society; 1983;3:755-793.
23. Rocchini AP, Moorehead C, Katch V, Key J, Finta KM. Forearm resistance vessel abnormalities and insulin resistance in obese adolescents. Hypertension. 1992;19:615-620. [Abstract/Free Full Text]
24. Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304:930-933. [Abstract]
25. Zimmermann BG. Adrenergic facilitation by angiotensin: does it serve a physiological function? Clin Sci. 1981;60:343-348. [Medline] [Order article via Infotrieve]
26. Frohlich ED, Messerli FH, Reisin E, Dunn FG. The problem of obesity and hypertension. Hypertension. 1983;5(suppl III): III-71-III-78.
27. Frohlich ED. Obesity and hypertension: hemodynamic aspects. Ann Epidemiol. 1991;1:287-293. [Medline] [Order article via Infotrieve]
28. Rocchini AP. Cardiovascular regulation in obesity-induced hypertension. Hypertension. 1992;19(suppl I):I-56-I-60.
29. Hypertension Detection and Follow-up Program Cooperative Group. Age, education and prevalence of hypertension. Am J Epidemiol. 1977;106:351-361. [Abstract/Free Full Text]
30. Stamler R, Stamler J, Riedlinger NF, Algera G, Roberts RH. Weight and blood pressure: findings in hypertension screening of 1 million Americans. JAMA. 1978;240:1607-1610. [Abstract]
31. Messerli FH, Numez BD, Ventura HO, Snyder DW. Overweight and sudden death. Arch Intern Med. 1987;147:1725-1728.[Abstract]

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				A. Aneja, F. El-Atat, S. I. McFarlane, and J. R. Sowers Hypertension and Obesity Recent Prog. Horm. Res., January 1, 2004; 59(1): 169 - 205. [Abstract] [Full Text]

				K. Rahmouni and W. G. Haynes Leptin and the Cardiovascular System Recent Prog. Horm. Res., January 1, 2004; 59(1): 225 - 244. [Abstract] [Full Text]

				R. Wolk, A. S.M. Shamsuzzaman, and V. K. Somers Obesity, Sleep Apnea, and Hypertension Hypertension, December 1, 2003; 42(6): 1067 - 1074. [Abstract] [Full Text] [PDF]

				G. Grassi, G. Seravalle, F. Quarti-Trevano, R. Dell'Oro, G. Bolla, and G. Mancia Effects of Hypertension and Obesity on the Sympathetic Activation of Heart Failure Patients Hypertension, November 1, 2003; 42(5): 873 - 877. [Abstract] [Full Text] [PDF]

				K. Masuo, H. Kawaguchi, H. Mikami, T. Ogihara, and M. L. Tuck Serum Uric Acid and Plasma Norepinephrine Concentrations Predict Subsequent Weight Gain and Blood Pressure Elevation Hypertension, October 1, 2003; 42(4): 474 - 480. [Abstract] [Full Text] [PDF]

				G. Grassi, G. Seravalle, C. Turri, G. Bertinieri, R. Dell'Oro, and G. Mancia Impairment of Thermoregulatory Control of Skin Sympathetic Nerve Traffic in the Elderly Circulation, August 12, 2003; 108(6): 729 - 735. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden American Association of Clinical Endocrinologists (AACE) Consensus Conference on the Insulin Resistance Syndrome: 25-26 August 2002, Washington, DC Diabetes Care, March 1, 2003; 26(3): 933 - 939. [Full Text] [PDF]

G. E. Alvarez, S. D. Beske, T. P. Ballard, and K. P. Davy Sympathetic Neural Activation in Visceral Obesity Circulation, November 12, 2002; 106(20): 2533 - 2536.