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(Hypertension. 1995;25:560-563.)
© 1995 American Heart Association, Inc.
Articles |
Sympathetic Activation in Obese Normotensive Subjects
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.
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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
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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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.
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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.
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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.
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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).
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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).
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HR,
expressed in beats per minute [b/min]) and in muscle sympathetic
nerve activity (
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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%).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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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 reduced6 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.
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References |
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 R. Vettor, R. Serra, R. Fabris, C. Pagano, and G. Federspil Effect of Sibutramine on Weight Management and Metabolic Control in Type 2 Diabetes: A meta-analysis of clinical studies Diabetes Care, April 1, 2005; 28(4): 942 - 949. [Abstract] [Full Text] [PDF]
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G. E. Alvarez, J. R. Halliwill, T. P. Ballard, S. D. Beske, and K. P. Davy Sympathetic neural regulation in endurance-trained humans: fitness vs. fatness J Appl Physiol, February 1, 2005; 98(2): 498 - 502. [Abstract] [Full Text] [PDF]
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G. Grassi, A. Vincenti, R. Brambilla, F. Q. Trevano, R. Dell'Oro, A. Ciro, G. Trocino, A. Vincenzi, and G. Mancia Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure Hypertension, November 1, 2004; 44(5): 727 - 731. [Abstract] [Full Text] [PDF]
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 D. D. Christou, P. Parker Jones, A. E. Pimentel, and D. R. Seals Increased abdominal-to-peripheral fat distribution contributes to altered autonomic-circulatory control with human aging Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1530 - H1537. [Abstract] [Full Text] [PDF]
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J. C. Frisbee Enhanced arteriolar {alpha}-adrenergic constriction impairs dilator responses and skeletal muscle perfusion in obese Zucker rats J Appl Physiol, August 1, 2004; 97(2): 764 - 772. [Abstract] [Full Text] [PDF]
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G. E. Alvarez, T. P. Ballard, S. D. Beske, and K. P. Davy Subcutaneous obesity is not associated with sympathetic neural activation Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H414 - H418. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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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]
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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]
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 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]
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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]
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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. [Abstract] [Full Text] [PDF]
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A. L. Birkenfeld, C. Schroeder, M. Boschmann, J. Tank, G. Franke, F. C. Luft, I. Biaggioni, A. M. Sharma, and J. Jordan Paradoxical Effect of Sibutramine on Autonomic Cardiovascular Regulation Circulation, November 5, 2002; 106(19): 2459 - 2465. [Abstract] [Full Text] [PDF]
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 J. Refsgaard, C. Thomsen, F. Andreasen, and O. Gotzsche Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure Eur J Heart Fail, August 1, 2002; 4(4): 445 - 453. [Abstract] [Full Text] [PDF]
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 C. Planes, M. Leroy, G. Fayet, P. Aegerter, A. Foucher, and B. Raffestin Exacerbation of sleep-apnoea related nocturnal blood-pressure fluctuations in hypertensive subjects Eur. Respir. J., July 1, 2002; 20(1): 151 - 157. [Abstract] [Full Text] [PDF]
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 M. L.G. Correia, W. G. Haynes, K. Rahmouni, D. A. Morgan, W. I. Sivitz, and A. L. Mark The Concept of Selective Leptin Resistance: Evidence From Agouti Yellow Obese Mice Diabetes, February 1, 2002; 51(2): 439 - 442. [Abstract] [Full Text] [PDF]
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S. D. Beske, G. E. Alvarez, T. P. Ballard, and K. P. Davy Reduced cardiovagal baroreflex gain in visceral obesity: implications for the metabolic syndrome Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H630 - H635. [Abstract] [Full Text] [PDF]
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G. Grassi, G. Seravalle, R. Dell'Oro, C. Turri, L. Pasqualinotto, M. Colombo, and G. Mancia Participation of the Hypothalamus-Hypophysis Axis in the Sympathetic Activation of Human Obesity Hypertension, December 1, 2001; 38(6): 1316 - 1320. [Abstract] [Full Text] [PDF]
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S. D. Beske, G. E. Alvarez, T. P. Ballard, and K. P. Davy Gender difference in cardiovagal baroreflex gain in humans J Appl Physiol, November 1, 2001; 91(5): 2088 - 2092. [Abstract] [Full Text] [PDF]
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N. I. Abate, Y. H. Mansour, M. Tuncel, D. Arbique, B. Chavoshan, A. Kizilbash, T. Howell-Stampley, W. Vongpatanasin, and R. G. Victor Overweight and Sympathetic Overactivity in Black Americans Hypertension, September 1, 2001; 38(3): 379 - 383. [Abstract] [Full Text] [PDF]
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 Y. Akehi, H. Yoshimatsu, M. Kurokawa, T. Sakata, H. Eto, S. Ito, and J. Ono VLCD-Induced Weight Loss Improves Heart Rate Variability in Moderately Obese Japanese Experimental Biology and Medicine, May 1, 2001; 226(5): 440 - 445. [Abstract] [Full Text]
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R. Bergholm, J. Westerbacka, S. Vehkavaara, A. Seppälä-Lindroos, T. Goto, and H. Yki-Järvinen Insulin Sensitivity Regulates Autonomic Control of Heart Rate Variation Independent of Body Weight in Normal Subjects J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1403 - 1409. [Abstract] [Full Text]
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M. Emdin, A. Gastaldelli, E. Muscelli, A. Macerata, A. Natali, S. Camastra, and E. Ferrannini Hyperinsulinemia and Autonomic Nervous System Dysfunction in Obesity : Effects of Weight Loss Circulation, January 30, 2001; 103(4): 513 - 519. [Abstract] [Full Text] [PDF]
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 S. Matthaei, M. Stumvoll, M. Kellerer, and H.-U. Häring Pathophysiology and Pharmacological Treatment of Insulin Resistance Endocr. Rev., December 1, 2000; 21(6): 585 - 618. [Abstract] [Full Text]
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C. Weyer, R. E. Pratley, S. Snitker, M. Spraul, E. Ravussin, and P. A. Tataranni Ethnic Differences in Insulinemia and Sympathetic Tone as Links Between Obesity and Blood Pressure Hypertension, October 1, 2000; 36(4): 531 - 537. [Abstract] [Full Text] [PDF]
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G. Grassi, G. Seravalle, R. Dell'Oro, C. Turri, G. B. Bolla, and G. Mancia Adrenergic and Reflex Abnormalities in Obesity-Related Hypertension Hypertension, October 1, 2000; 36(4): 538 - 542. [Abstract] [Full Text] [PDF]
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K. Narkiewicz and V. K. Somers Interactive Effect of Heart Rate and Muscle Sympathetic Nerve Activity on Blood Pressure Circulation, December 21, 1999; 100(25): 2514 - 2518. [Abstract] [Full Text] [PDF]
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L. Tiret, O. Poirier, V. Hallet, T. A. McDonagh, C. Morrison, J. J. V. McMurray, H. J. Dargie, D. Arveiler, J.-B. Ruidavets, G. Luc, et al. The Lys198Asn Polymorphism in the Endothelin-1 Gene Is Associated With Blood Pressure in Overweight People Hypertension, May 1, 1999; 33(5): 1169 - 1174. [Abstract] [Full Text] [PDF]
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K. Narkiewicz, C. A. Pesek, M. Kato, B. G. Phillips, D. E. Davison, and V. K. Somers Baroreflex Control of Sympathetic Nerve Activity and Heart Rate in Obstructive Sleep Apnea Hypertension, December 1, 1998; 32(6): 1039 - 1043. [Abstract] [Full Text] [PDF]
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K. P. Davy, H. Tanaka, E. A. Andros, J. G. Gerber, and D. R. Seals Influence of age on arterial baroreflex inhibition of sympathetic nerve activity in healthy adult humans Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1768 - H1772. [Abstract] [Full Text] [PDF]
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K. Narkiewicz, P. J. H. van de Borne, R. L. Cooley, M. E. Dyken, and V. K. Somers Sympathetic Activity in Obese Subjects With and Without Obstructive Sleep Apnea Circulation, August 25, 1998; 98(8): 772 - 776. [Abstract] [Full Text] [PDF]
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E. Muscelli, M. Emdin, A. Natali, L. Pratali, S. Camastra, A. Gastaldelli, S. Baldi, C. Carpeggiani, and E. Ferrannini Autonomic and Hemodynamic Responses to Insulin in Lean and Obese Humans J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2084 - 2090. [Abstract] [Full Text]
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G. Grassi, G. Seravalle, M. Colombo, G. Bolla, B. M. Cattaneo, F. Cavagnini, and G. Mancia Body Weight Reduction, Sympathetic Nerve Traffic, and Arterial Baroreflex in Obese Normotensive Humans Circulation, May 26, 1998; 97(20): 2037 - 2042. [Abstract] [Full Text] [PDF]
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G. Grassi, M. Colombo, G. Seravalle, D. Spaziani, and G. Mancia Dissociation Between Muscle and Skin Sympathetic Nerve Activity in Essential Hypertension, Obesity, and Congestive Heart Failure Hypertension, January 1, 1998; 31(1): 64 - 67. [Abstract] [Full Text] [PDF]
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G. Grassi, B. M. Cattaneo, G. Seravalle, A. Lanfranchi, and G. Mancia Baroreflex Control of Sympathetic Nerve Activity in Essential and Secondary Hypertension Hypertension, January 1, 1998; 31(1): 68 - 72. [Abstract] [Full Text] [PDF]
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M. Vaz, G. Jennings, A. Turner, H. Cox, G. Lambert, and M. Esler Regional Sympathetic Nervous Activity and Oxygen Consumption in Obese Normotensive Human Subjects Circulation, November 18, 1997; 96(10): 3423 - 3429. [Abstract] [Full Text]
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G. Grassi, B. M. Cattaneo, G. Seravalle, A. Lanfranchi, M. Pozzi, A. Morganti, S. Carugo, and G. Mancia Effects of Chronic ACE Inhibition on Sympathetic Nerve Traffic and Baroreflex Control of Circulation in Heart Failure Circulation, August 19, 1997; 96(4): 1173 - 1179. [Abstract] [Full Text]
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J. R. Sowers Insulin and Insulin-Like Growth Factor in Normal and Pathological Cardiovascular Physiology Hypertension, March 1, 1997; 29(3): 691 - 699. [Full Text]
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G. Grassi, B. M. Cattaneo, G. Seravalle, A. Lanfranchi, G. Bolla, and G. Mancia Baroreflex Impairment by Low Sodium Diet in Mild or Moderate Essential Hypertension Hypertension, March 1, 1997; 29(3): 802 - 807. [Abstract] [Full Text]
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A. A. Mangoni, C. Giannattasio, A. Brunani, M. Failla, M. Colombo, G. Bolla, F. Cavagnini, G. Grassi, and G. Mancia Radial Artery Compliance in Young, Obese, Normotensive Subjects Hypertension, December 1, 1995; 26(6): 984 - 988. [Abstract] [Full Text]
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G. Grassi, G. Seravalle, B. M. Cattaneo, A. Lanfranchi, S. Vailati, C. Giannattasio, A. Del Bo, C. Sala, G. B. Bolla, M. Pozzi, et al. Sympathetic Activation and Loss of Reflex Sympathetic Control in Mild Congestive Heart Failure Circulation, December 1, 1995; 92(11): 3206 - 3211. [Abstract] [Full Text]
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