Diet and Exercise Training Restore Blood Pressure and Vasodilatory Responses During Physiological...

Diet and Exercise Training Restore Blood Pressure andVasodilatory Responses During Physiological Maneuvers in

Obese ChildrenMaurício M. Ribeiro, MS; Alexandre G. Silva; Nelson S. Santos; Isabel Guazzelle;

Luciana N.J. Matos, MD, PhD; Ivani C. Trombetta, PhD; Alfredo Halpern, MD, PhD;Carlos E. Negrão, PhD; Sandra M.F. Villares, MD, PhD

Background—The effects of diet and diet plus exercise training on muscle vasodilatation during physiological maneuversin obese children are unknown. We tested the hypothesis that (1) blood pressure (BP) and forearm vascular conductance(FVC) responses during handgrip exercise and mental stress would be altered in obese children and (2) diet plus exercisetraining would restore BP and FVC responses during exercise and mental stress in obese children.

Methods and Results—Thirty-nine obese children (aged 10�0.2 years) were randomly divided into 2 groups: diet plusexercise training (n�21; body mass index [BMI]�28�0.5 kg/m2) and diet (n�18; BMI�30�0.4 kg/m2). Tenage-matched lean control children (BMI�17�0.5 kg/m2) were also studied. Forearm blood flow was measured byvenous occlusion plethysmography. BP was monitored noninvasively. Handgrip exercise was performed at 30%maximal voluntary contraction for 3 minutes. Stroop color word test was performed for 4 minutes. Baseline BP wassignificantly higher and FVC was significantly lower in obese children. During exercise and mental stress, BP responseswere significantly higher and FVC responses were significantly lower in obese children. Diet and diet plus exercisetraining significantly reduced body weight. Diet and diet plus exercise training significantly decreased BP levels duringexercise and mental stress. Diet plus exercise training, in contrast to diet alone, significantly increased FVC responsesduring exercise (3.7�0.3 versus 5.6�0.4 U; P�0.01) and mental stress (3.5�0.5 versus 4.5�0.4 U; P�0.02). After dietplus exercise training, BP and FVC responses during exercise and mental stress were similar between obese childrenand the control group.

Conclusions—Obesity exacerbates BP responses and impairs FVC responses during exercise and mental stress in children.Diet and exercise training restore BP and FVC responses in obese children. (Circulation. 2005;111:1915-1923.)

Key Words: obesity � children � blood pressure � muscles � vasodilatation

Obesity has been considered one of the most worrisomehealth problems in occidental countries. More dramatic

is that this epidemic has reached young individuals. The rateof obesity in children and adolescents has doubled in the past3 decades in the United States.1,2 These statistics havedirected our attention to a new challenge in human obesity.

In recent years, our understanding about the implications ofadulthood obesity has improved considerably. We havelearned that cardiovascular functioning and regulatory mech-anisms are altered substantially in human obesity. Musclesympathetic nerve activity is increased during exercise andmental stress in obese individuals.3,4 In contrast, the reflex-ively mediated increase in muscle blood flow during thesephysiological maneuvers is attenuated in obese individuals.During the cold pressor test, muscle sympathetic nerveactivity and muscle vascular resistance are increased in obese

women compared with lean women.4 These neurovascularalterations seem to be linked to the exacerbated bloodpressure levels during sympathoexcitation. However, hemo-dynamic regulation during physiological maneuvers in child-hood obesity is poorly understood.

Hypocaloric diet and exercise training have been recom-mended as a nonpharmacological treatment to obese adultindividuals. This regimen reduces body weight, preserveslean body mass, and improves insulin sensitivity.5 In addition,diet plus exercise training, in contrast to diet alone, improvesmuscle vasodilatation during exercise in obese adult individ-uals.5 However, the effects of diet and/or exercise training onmuscle vasodilatory responses during exercise and mentalchallenge in children with obesity are unknown.

In the present study we tested the hypothesis that (1) bloodpressure responses and muscle vasodilatory responses to

Received November 5, 2004; revision received December 20, 2004; accepted December 28, 2004.From the Department of Endocrinology, Medical School (M.M.R., A.G.S., N.S.S., I.G., A.H., S.M.F.V.); Heart Institute (InCor), Medical School

(A.G.S., L.N.J.M., I.C.T., C.E.N.); and School of Physical Education and Sport (C.E.N.), University of São Paulo, São Paulo, Brazil.Correspondence to Maurício M. Ribeiro, MS, Unidade de Obesidade e Laboratório de Nutrição Humana e Doenças Metabólicas, LIM 25, Faculdade

de Medicina da Universidade de São Paulo, Av Dr Arnaldo 455, Sala 4305, CEP 05403-900, São Paulo, SP Brasil. E-mail [email protected]© 2005 American Heart Association, Inc.

Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000161959.04675.5A

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handgrip exercise and mental stress would be altered in obesechildren compared with lean children and (2) hypocaloric dietand exercise training in obese children would have greatereffects on blood pressure responses and muscle vasodilatoryresponses during exercise and mental stress than diet alone.

MethodsStudy PopulationAfter written informed consent was obtained, 39 consecutive outpa-tient children from the Obesity Ambulatory of the EndocrinologyDepartment, University of São Paulo Medical School, meeting thefollowing inclusion/exclusion criteria were offered participation inthe study: (1) age between 8 and 12 years; (2) body mass index(BMI) �95%; (3) no medication; (4) no evidence of metabolic,hormonal, and cardiovascular disease at the time of the study; and (5)no engagement in an exercise program. These children were ran-domly divided into 2 groups: hypocaloric diet plus exercise training(n�21; BMI 23 to 35 kg/m2, z score BMI 2.8 to 6.13) andhypocaloric diet (n�18; BMI 24 to 35 kg/m2, z score BMI 2.8 to6.37). Obesity was defined according to the age- and sex-specificBMI cutoff criteria recently described.6 Ten age-matched normalcontrol lean children were also studied (BMI 16 to 19 kg/m2). Thestudy protocol was approved by the Human Subject ProtectionCommittees of the Heart Institute and Clinical Hospital, School ofMedicine, University of São Paulo.

Measurements and Procedures

Anthropometric MeasurementsBody weight was measured with an electronic body weight scalewith children dressed in a light T-shirt and shorts. Height wasmeasured by Harpenden stadiometer. The body weight status wasrecorded as BMI and z score of BMI with the use of the LMSmethod.7

Forearm Blood FlowForearm blood flow was measured by venous occlusion plethysmog-raphy.8 The nondominant arm was elevated above heart level toensure adequate venous drainage. A mercury-filled silastic tubeattached to a low-pressure transducer was placed around the forearmand connected to a plethysmograph (Hokanson). Sphygmomanome-ter cuffs were placed around the wrist and upper arm. At 15-secondintervals, the upper cuff was inflated above venous pressure for 7 to8 seconds. Forearm blood flow (mL/min per 100 g) was determinedon the basis of a minimum of 4 separate readings. Forearm vascularconductance was calculated by dividing forearm blood flow by meanarterial pressure. The reproducibility of forearm blood flow mea-sured at different time intervals in the same individual expressed asmL/min per 100 mL tissue in our laboratory is r�0.93.

Blood Pressure and Heart RateDuring mental stress, mean blood pressure was monitored noninva-sively by a finger photoplethysmograph device (Finapress 2300;Ohmeda) on a beat-to-beat basis (AT/CODAS) at a frequency of 500Hz. During handgrip exercise, mean blood pressure was monitorednoninvasively and intermittently from an automatic and oscillomet-ric cuff (DX 2710, Dixtal) placed on the ankle with cuff widthadjusted to ankle circumference. Mean blood pressure was chosenbecause this parameter is measured accurately by the automatic andoscillometric device. The cuff inflated every 30 seconds. Heart ratewas monitored continuously through lead II of the ECG.

Handgrip ExerciseAfter the maximal voluntary contraction (mean of 3 trials) wasobtained, static handgrip exercise was performed with the dominantarm with the use of a handgrip dynamometer.3 Children wereinstructed to breathe normally during exercise and to avoid inadver-tent performance of a Valsalva maneuver.

Mental Stress TestingMental stress was elicited by the Stroop color word test.9 During theStroop color word test, subjects were shown a series of names ofcolors written in a different color of ink from the color specified. Thechildren were asked to identify the color of the ink, not read theword.

Insulin ResistancePlasma insulin levels were determined by an immunofluorometricAutoDELFIA device (Wallac Oy). Insulin resistance was estimatedby homeostasis model assessment (HOMA score) and calculatedwith the following formula: fasting serum insulin (�U/mL)�fastingplasma glucose (mmol/L)/22.5.10

Blood ChemistryBlood samples were collected to determine concentrations of cho-lesterol and subfractions (LDL and HDL cholesterol), triglycerides,and fasting blood glucose. Enzymatic calorimetric assays were usedto analyze cholesterol and subfractions and glucose levels.

Dietary ProtocolThe basal energy requirements were estimated during the Food andAgriculture Organization/World Health Organization/United Na-tions University11 equation multiplied by a factor of 1.3. During 16weeks, energy intake was 1400 kcal/d. The hypocaloric diet con-sisted of 50% to 70% carbohydrates, 10% to 15% protein, and 15%to 30% fat. On alternate weeks, every child visited the clinicalnutritionist for a regular checkup. On each visit, the children wereweighed and encouraged to record their intake to ensure adherence tothe dietary protocol. The expected weight loss was �5% to 10% ofthe initial weight.

Exercise TrainingExercise training consisted of three 60-minute exercise sessions perweek during 4 months. Each exercise session consisted of 30 minutesof walking and/or jogging and 30 minutes of recreational exercise.The exercise intensity was established by heart rate levels thatcorresponded to an anaerobic threshold up to 10% below therespiratory compensation point obtained in a progressive cardiopul-monary exercise test. The anaerobic threshold was determined tooccur at the point where there was a loss of linearity between oxygenuptake and carbon dioxide production or at the point where theventilatory equivalent for oxygen or end-tidal oxygen partial pres-sure curves reached their respective minimum values and began torise during the progressive exercise test.12 The respiratory compen-sation point was determined as the point where the ventilatoryequivalent for carbon dioxide was the lowest before a systematicincrease or where end-tidal carbon dioxide partial pressure reached amaximum value and began to decrease.13 The peak oxygen uptakewas considered at the end of the cardiopulmonary exercise test ontreadmill (ramp protocol with increments every minute up toexhaustion).

Experimental Protocol

Protocol 1: Handgrip ExerciseThe arm was positioned for venous plethysmography. Baselineforearm blood flow, mean blood pressure, and heart rate wererecorded for 3 minutes. Handgrip isometric exercise was performedfor 3 minutes at 30% of maximal voluntary contraction. Bloodpressure, forearm blood flow, and heart rate were recorded contin-uously during handgrip exercise.

Protocol 2: Mental StressBaseline forearm blood flow, mean blood pressure, and heart ratewere recorded for 3 minutes. Mental stress was performed for 4minutes. Blood pressure, forearm blood flow, and heart rate wererecorded continuously during mental stress. The task difficulty wasdetermined on completion of the protocol with the use of a standard5-point scale: 0, not stressful; 1, somewhat stressful; 2, stressful; 3,very stressful; and 4, very very stressful.

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Statistical AnalysisThe possible differences between obese children and lean childrenwere tested by unpaired t test. Two-way ANOVA with repeatedmeasures was performed to test (1) the differences between obesechildren and lean children during handgrip exercise and mentalstress; (2) the resting differences between obese children subjected toa diet and obese children subjected to a diet plus exercise training;and (3) the differences between obese children subjected to a diet ordiet plus exercise training and lean children. Three-way ANOVAwith repeated measures was performed to test the differencesbetween obese children subjected to a diet or diet plus exercisetraining during handgrip exercise and mental stress. When signifi-cance was found, the Scheffé post hoc comparison was performed.The data are presented as mean�SE. P�0.05 was consideredstatistically significant.

ResultsEffects of Obesity

Baseline MeasurementsAnthropometric and hemodynamic characteristics in obeseand lean children are shown in Table 1. Age and height weresimilar in obese and lean children. Body weight and BMIwere significantly higher in obese children. Peak V̇O2 wassignificantly lower in obese children. In regard to hemody-namic measurements, mean blood pressure was significantlyincreased in obese children compared with lean children.Forearm blood flow and forearm vascular conductance weresignificantly lower in obese children.

Handgrip ExerciseMean blood pressure increased progressively and signifi-cantly during handgrip exercise in obese children but not inlean children in whom mean blood pressure was unchanged(Figure 1). The comparisons between groups showed that themagnitude of mean blood pressure responses during exercise,analyzed by the interaction of phase effect and time effect,was significantly higher in obese children (P�0.005; Figure1). Heart rate increased significant and similarly duringhandgrip exercise in both groups studied (Table 2). Forearmblood flow increased significantly during handgrip exercisein lean children (Table 2). In contrast, forearm blood flowwas unchanged during exercise in obese children (Table 2).Forearm vascular conductance increased significantly duringhandgrip exercise in lean children but not in obese children

(Figure 2). The comparisons between groups showed that themagnitude of forearm blood flow and forearm vascularconductance responses during exercise, analyzed by theinteraction of phase effect and time effect, was significantlylower in obese children compared with lean children(P�0.01, P�0.02, respectively; Table 2, Figure 2).

Mental StressIn obese children, mean blood pressure increased progres-sively and significantly during mental stress (Figure 1). Inlean children, mean blood pressure during mental stress wasunchanged (Figure 1). The comparisons between groupsshowed that the magnitude of mean blood pressure responsesduring mental stress, analyzed by the interaction of phaseeffect and time effect, was significantly higher in obesechildren than in lean children (P�0.01; Figure 1). Heart rateincreased significantly and similarly during mental stress inboth groups studied (Table 2). During mental stress, forearmblood flow increased significantly in lean children but not inobese children, in whom forearm blood flow was unchanged(Table 2). Similarly, forearm vascular conductance increasedsignificantly during mental stress in lean children (Figure 2).In contrast, in obese children, forearm vascular conductancewas unchanged during mental stress (Figure 2). The compar-isons between groups showed that the magnitude of forearmblood flow and forearm vascular conductance responsesduring mental stress, analyzed by the interaction of phaseeffect and time effect, was significantly lower in obesechildren than in lean children (P�0.01 and P�0.02, respec-tively; Table 2, Figure 2).

TABLE 1. Anthropometric and Hemodynamic Characteristics inObese Children

Lean Obese P

Age, y 10�0.3 10�0.2 0.48

Weight, kg 35�1.2 63�1.2 0.00

Height, m 1.4�0.1 1.5�0.2 0.40

BMI, kg/m2 17�0.5 29�0.3 0.00

V̇O2, mL � kg�1 � min�1 34�0.3 23�0.8 0.03

MBP, mm Hg 71�3.1 79�2.2 0.04

HR, bpm 81�3.1 81�2.0 0.70

FBF, mL � min�1 � 100 g�1 3.7�0.4 2.5�0.1 0.03

FVC, U 5.1�0.3 3.2�0.1 0.00

MBP indicates mean blood pressure; HR, heart rate; FBF, forearm blood flow;and FVC, forearm vascular conductance.

Figure 1. Mean blood pressure during static handgrip exerciseand mental stress in obese and lean children. Note that meanblood pressure responses during both static handgrip exerciseand mental stress are significantly increased in obese children.*P�0.05 vs rest; †P�0.05 vs lean.

Ribeiro et al Muscular Vasodilation in Obese Children 1917



Effects of Diet and Exercise Training

Baseline MeasurementsAnthropometric and metabolic characteristics before andafter diet plus exercise training and diet alone are shown inTable 3. Before interventions, age, body weight, height, BMI,z score of BMI, total cholesterol, HDL cholesterol, LDLcholesterol, and glucose levels were similar between obesechildren randomized to diet plus exercise training or dietalone. Triglycerides and insulin levels were higher in the dietgroup compared with the diet plus exercise training group.The HOMA score was not different in the diet group and thediet plus exercise training group.

Diet plus exercise training significantly decreased bodyweight, BMI, z score of BMI, total cholesterol, triglycerides,glucose and insulin levels, and HOMA score. Diet plusexercise training significantly increased HDL cholesterollevels and peak V̇O2. Diet plus exercise training tended todecrease LDL cholesterol (P�0.08). Diet significantly de-creased body weight, BMI, z score of BMI, total cholesterol,

triglycerides, glucose and insulin levels, and HOMA score.Diet caused no changes in HDL cholesterol, LDL cholesterol,and peak V̇O2. The comparisons between groups showed thatbody weight, BMI, z score of BMI, total cholesterol, glucoselevels, and HOMA score were similar in children subjected todiet plus exercise training and diet alone. However, HDLcholesterol levels and peak V̇O2 were significantly higher inthe diet plus exercise training group compared with the dietalone group. In addition, insulin and triglyceride levels werelower in the diet plus exercise training group.

The hemodynamic measurements before and after inter-ventions are shown in Tables 4 and 5. Before interventions,there were no differences between groups.

Diet plus exercise training or diet alone significantlyreduced resting mean blood pressure. Diet plus exercisetraining significantly decreased resting heart rate, but dietcaused no change in heart rate. Diet plus exercise trainingsignificantly increased forearm blood flow and forearm vas-cular conductance. Diet did not change forearm blood flowand forearm vascular conductance. The comparisons betweengroups showed that mean blood pressure was similar in thediet plus exercise training group and the diet group. Heart ratewas also similar between groups. In contrast, forearm bloodflow was significantly higher in the diet plus exercise traininggroup than in the diet group. Similarly, forearm vascularconductance was significantly higher in the diet plus exercisetraining group. Further analysis showed that resting meanblood pressure in obese children subjected to diet plusexercise training or diet alone was similar to that found inlean children (P�0.07; Figure 3). In addition, the differencein resting forearm vascular conductance between obese chil-dren subjected to diet plus exercise training and lean childrenwas no longer observed (P�0.10; Figure 4). In contrast,resting forearm vascular conductance remained significantlylower in obese children subjected to diet alone compared withlean children (Figure 4).

Handgrip Exercise and Mental StressThe hemodynamic measurements during handgrip exerciseand mental stress after interventions are shown in Tables 4and 5. Before interventions, there were no significant differ-ences between groups.

Diet plus exercise training or diet alone significantlyreduced mean blood pressure levels during handgrip exercise

Figure 2. Forearm vascular conductance during static handgripexercise and mental stress in obese and lean children. Note thatforearm vascular conductance responses during both statichandgrip exercise and mental stress are significantly decreasedin obese children. *P�0.05 vs rest; †P�0.05 vs lean.

TABLE 2. Hemodynamic Responses in Obese Children and Lean Children During Handgrip Exercise andMental Stress

Handgrip Exercise Mental Stress

Rest 1 min 2 min 3 min Rest 1 min 2 min 3 min 4 min

HR, bpm

Lean 81�3 84�3* 88�3* 92�3* 83�3 86�2* 87�3* 86�3* 86�3*

Obese 81�2 85�2* 89�2* 90�2* 78�1 82�3* 83�1* 84�2* 83�2*

FBF, mL � min�1 � 100 g�1

Lean 3.7�0.4 4.5�0.6* 5.2�0.4* 5.1�0.5* 3.4�0.4 3.6�0.6 3.9�0.4* 4.2�0.4* 4.3�0.4*

Obese 2.5�0.1† 2.7�0.2† 2.8�0.2† 3.1�0.1† 2.3�0.1† 2.4�0.2† 2.5�0.2† 2.6�0.2† 2.6�0.2†

HR indicates heart rate; FBF, forearm blood flow.*P�0.05 vs rest; †P�0.05 vs lean.




and mental stress. Diet plus exercise training significantlydecreased heart rate levels during handgrip exercise andmental stress. Diet alone did not change heart rate levelsduring handgrip exercise and mental stress. Diet plus exercisetraining provoked a significant increase in the magnitude offorearm blood flow and forearm vascular conductance re-sponses during handgrip exercise and mental stress. Incontrast, diet alone caused no change in the magnitude offorearm blood flow and forearm vascular conductance re-sponses during handgrip exercise and mental stress. Thecomparisons between groups showed that the magnitude ofmean blood pressure responses during handgrip exercise andmental stress was similar in diet plus exercise training anddiet groups. Heart rate during handgrip exercise and mentalstress was not different in diet plus exercise training and dietgroups. The magnitude of forearm blood flow responsesduring exercise and mental stress, analyzed by the interactionof phase effect, time effect, and group effect, was signifi-cantly higher in the diet plus exercise training group com-pared with the diet group (exercise: P�0.009; mental stress:P�0.008). Similarly, the magnitude of forearm vascularconductance responses during exercise and mental stress wassignificantly higher in the diet plus exercise training groupthan in the diet group (exercise: P�0.001; mental stress:P�0.001).

Further analysis showed that the difference in mean bloodpressure during handgrip exercise and mental stress in obesechildren subjected to diet plus exercise training or diet andlean children was no longer observed (exercise: P�0.07;mental stress: P�0.08; Figure 3). In the diet plus exercisetraining group, the magnitude of forearm vascular conduc-tance responses during exercise and mental stress increasedsignificantly toward the level found in the lean group (Figure4). Thus, the differences in forearm vascular conductanceduring exercise and mental stress between obese childrensubjected to diet plus exercise training and lean children wereno longer found (exercise: P�0.10; mental stress: P�0.10;

Figure 4). In contrast, the magnitude of forearm vascularconductance responses during exercise and mental stressremained significantly lower in obese children subjected to adiet compared with lean children (Figure 4).

DiscussionThe main and new findings of the present study are asfollows: (1) blood pressure responses during static handgripexercise and mental stress are exacerbated in obese children;(2) muscle vasodilatory responses during static handgripexercise and mental stress are blunted in obese children; (3)diet plus exercise training or diet reduces blood pressureresponses during static handgrip exercise and mental stresstoward normal levels; and (4) diet plus exercise training, incontrast to diet alone, improves muscle vasodilatory re-sponses during static handgrip exercise and mental stress inobese children.

Impact of Obesity on Hemodynamic ResponsesThe link between obesity and high blood pressure, hypertri-glyceridemia, and increased fasting insulin levels has beenreported consistently in children.14,15 Our study confirms theincreased blood pressure levels in obese children comparedwith lean children. Moreover, our study shows that obesechildren have augmented blood pressure responses duringexercise and mental stress. This increased pressor response inobese children may be due to abnormal neurovascular controlduring physiological maneuvers. In obese adult individuals,muscle sympathetic nerve activity is increased during exer-cise and mental stress. This sympathetic activation seems toincrease muscle peripheral vascular resistance and, in conse-quence, blood pressure.16 Despite the fact that muscle sym-pathetic nerve activity has not been measured in our study, wecan suspect that sympathetic nerve activity was increased inobese children. On the other hand, the possibility of increasedcardiac output has been suggested to explain high bloodpressure in obese children. Our results do not support this

TABLE 3. Anthropometric and Metabolic Characteristics in Obese ChildrenSubjected to Diet or Diet Plus Exercise Training

Diet Diet Plus Exercise Training

Before After Before After

Age, y 10�0.3 10�0.3 10�0.2 10�0.2

Weight, kg 66�1.2 61�1.1* 61�1.3 54�1.1*

Height, m 1.5�0.1 1.5�0.2 1.5�0.2 1.5�0.2

BMI, kg/m2 30�0.4 27�0.5* 28�0.5 25�0.5*

z score BMI 4.6�0.2 3.5�0.3* 4.5�0.3 3.0�0.3*†

V̇O2 peak, mL � kg�1 � min�1 23�0.8 25�1.0 24�0.7 31�0.8*

Glucose, mg/dL 87�1.0 82�1.8* 89�1.0 84�1.0*

Insulin, �U/mL 23�1.0 11�1.1* 14�0.5† 9�0.6*†

HOMA score 4.5�1.2 2.5�0.6* 3.5�0.3 2.1�0.5*

Cholesterol, mg/dL 181�6.0 174�5.0* 167�5.0 152�4.0*

HDL cholesterol, mg/dL 40�0.6 40�0.6 39�0.8 44�0.5*†

LDL cholesterol, mg/dL 114�1.3 113�1.4 106�1.2 92�1.1

Triglycerides, mg/dL 131�1.5 103�1.6* 91�1.4† 84�1.5*†

*P�0.05 vs before; †P�0.05 vs diet.




assumption because heart rate responses to exercise andmental stress were similar in obese children and lean children.

The reduction in resting muscle blood flow and musclevasodilatory responses during physiological maneuvers hasbeen well characterized in obese adolescents and adults.5,17 Inthe present study we found that the reduction in restingmuscle blood flow associated with obesity takes place muchearlier in the human life span than we thought. Restingforearm blood flow is substantially decreased in 8- to 12-year-old children. In addition, childhood obesity impairsmuscle vasodilatory responses during exercise and mentalstress. These findings suggest not only regional blood flowalteration but also vascular dysfunction in children. Thisabnormal muscle vasodilatation during physiological maneu-vers is consistent with a previous report that showed loweredvasodilatation during reactive hyperemia in obese children.18

Effects of Diet and Exercise Training onHemodynamic ResponsesFour months of diet plus exercise training provoked asignificant reduction in body weight and BMI and a signifi-

cant increase in functional capacity in obese children. Inaddition, this regimen had favorable effects on the metabolicprofile. However, the most remarkable finding of our study isthe fact that diet plus exercise training significantly increasedmuscle vasodilatation during exercise and mental stress inobese children. This increase was so dramatic that the musclevasodilatation during these physiological maneuvers reachednormal levels. After diet plus exercise training, the differ-ences in vasodilatory responses between obese children andlean children were no longer observed. Although diet alonereduces body weight and BMI, it does not change musclevasodilatation during exercise and mental stress. Taken to-gether, these results are consistent with the inherent effects ofexercise training on blood vessel functioning in obese chil-dren. Moreover, they show that diet alone is insufficient torestore resting muscle blood flow and muscle vasodilatoryresponses in obese children. The improvement in blood vesselfunctioning after diet plus exercise training in obese childrenhas been also reported during reactive hyperemia.19 Theseinvestigators observed that diet and exercise improved calf

TABLE 4. Hemodynamic Responses in Obese Children Subjected to Diet or DietPlus Exercise Training During Handgrip Exercise

Rest 1 min 2 min 3 min

MBP, mm Hg

Diet

Before 78�2 82�3* 86�3* 90�2*

After 75�2† 84�2*† 83�2*† 86�3*†

Diet�ET

Before 80�2 83�1* 90�1* 94�2*

After 75�1† 80�1*† 85�2*† 85�2*†

HR, bpm

Diet

Before 81�3 85�3* 89�3* 90�3*

After 75�3 78�3* 82�3* 84�3*

Diet�ET

Before 82�3 84�3* 88�3* 90�3*

After 73�3† 77�3*† 79�3*† 81�3*†

FBF, mL � min�1 � 100 g�1

Diet

Before 2.2�0.2 2.5�0.2 2.5�0.2 2.7�0.2

After 2.3�0.2 2.4�0.2 2.6�0.2 2.8�0.2

Diet�ET

Before 2.7�0.1 2.9�0.1 3.1�0.2 3.4�0.2

After 3.3�0.2†‡ 3.8�0.2*†‡ 4.2�0.2*†‡ 4.6�0.2*†‡

FVC, U

Diet

Before 3.0�0.1 3.0�0.1 3.1�0.1 3.0�0.1

After 2.8�0.2 2.9�0.2 3.1�0.1 3.4�0.2

Diet�ET

Before 3.4�0.1 3.4�0.1 3.5�0.2 3.5�0.2

After 4.4�0.1*†‡ 4.8�0.2*†‡ 5.1�0.1*†‡ 5.5�0.3*†‡

MBP indicates mean blood pressure; HR, heart rate; FBF, forearm blood flow; and ET, exercisetraining.

*P�0.05 vs rest; †P�0.05 vs before; ‡P�0.05 vs after diet.




vasodilatation during hyperemia. Moreover, these effectswere lost after discontinuation of exercise training.

The mechanisms involved in the vasodilatory responsesduring exercise and mental stress after diet plus exercisetraining in obese children are outside the scope of the presentstudy. However, we can speculate that diet plus exercisetraining improves endothelial function. First, the increase inmuscle blood flow during exercise and mental stress inhumans is, in great part, endothelially mediated. Second,exercise training substantially improves endothelial functionin skeletal muscle and cardiac muscle in humans.20,21 Alter-natively, diet and exercise training may reduce musclesympathetic nerve activity in obese children. The attenuationin sympathetic nerve activity would improve forearm vascu-lar responsiveness during mental stress and exercise bydecreasing the muscle vasoconstrictor force. It is also possi-ble that the attenuation in sympathetic activation may havereversed the structural changes in resistance vessels that, inturn, favor the increase in forearm vascular conductanceduring physiological maneuvers. In a recent study we found

that diet plus exercise training significantly reduced musclesympathetic nerve activity in obese adult individuals.5 More-over, muscle vasodilatation in response to handgrip exercisewas significantly increased after diet plus exercise training.5

Another important finding in our study is related to bloodpressure. In agreement with previous studies,22 body weightloss significantly reduced blood pressure in obese children.The novelty of our study is that body weight loss by diet plusexercise training or diet alone significantly reduced bloodpressure levels during handgrip exercise and mental stresstoward normal levels in obese children. It is unlikely that thereduction in blood pressure was due to heart rate because itwas similar in diet plus exercise training and diet alonegroups. We did not measure stroke volume or blood volumein the present study. Therefore, we do not know whether thereduction in blood pressure was due to any change in cardiacoutput. Thus, we can suggest that blood pressure reductionwas associated with neurovascular sympathetic attenuation.

The 2 interventions, diet and diet plus exercise training,provoked a significant reduction in plasma insulin levels and

TABLE 5. Hemodynamic Responses in Obese Children Subjected to a Diet orDiet Plus Exercise Training During Mental Stress

Rest 1 min 2 min 3 min 4 min

MBP, mm Hg

Diet

Before 83�3 87�4* 91�4* 93�3* 95�4*

After 76�2† 86�2*† 86�2*† 86�2*† 89�2*†

Diet�ET

Before 79�3 83�3* 86�3* 87�1* 86�2*

After 73�1† 78�2*† 82�1*† 81�1*† 83�2*†

HR, bpm

Diet

Before 81�3 87�3* 88�3* 89�3* 92�3*

After 74�3 79�3* 82�3* 83�3* 82�3*

Diet�ET

Before 82�3 86�3* 85�3* 87�3* 86�3*

After 73�3† 76�3*† 78�3*† 79�3*† 77�3*†

FBF, mL � min�1 � 100 g�1

Diet

Before 2.1�0.2 2.3�0.2 2.3�0.2 2.5�0.2 2.5�0.2

After 2.2�0.1 2.3�0.1 2.4�0.1 2.5�0.1 2.4�0.1

Diet�ET

Before 2.6�0.1 2.6�0.1 2.8�0.2 2.7�0.1 2.8�0.1

After 3.3�0.2†‡ 4.2�0.2*†‡ 4.4�0.2*†‡ 4.6�0.3*†‡ 4.1�0.2*†‡

FVC, U

Diet

Before 2.6�0.2 2.7�0.2 2.7�0.2 2.9�0.1 2.8�0.1

After 2.9�0.1 2.7�0.1 2.8�0.1 3.0�0.1 2.8�0.1

Diet�ET

Before 3.3�0.1 3.2�0.1 3.3�0.2 3.1�0.1 3.2�0.1

After 4.6�0.1†‡ 5.4�0.2*†‡ 5.4�0.1*†‡ 5.6�0.1*†‡ 5.0�0.1*†‡

MBP indicates mean blood pressure; HR, heart rate; FBF, forearm blood flow; and ET, exercisetraining.

*P�0.05 vs rest; †P�0.05 vs before; ‡P�0.05 vs after diet.




HOMA score. Despite the fact that these findings are asso-ciated with improvement in insulin sensitivity in children andadolescents,17,23 they may simply be a consequence of reduc-tion in body fat.

LimitationsWe recognize several limitations in our study. We have notincluded an obese trained group in our study. However, wecan suggest that exercise training alone would have improvedmuscle vasodilatory responses during static handgrip exerciseand mental stress in obese children. A recent study showedthat flow-mediated dilation of the brachial artery was im-proved after exercise training in obese children despite thefact that body weight and BMI were unchanged.24 The normalcontrol lean children were not subjected to exercise training.Thus, we do not know the effects of exercise training in ourlean control group. The augmented forearm blood flowresponses in children subjected to diet plus exercise trainingcould be attributed to the workload during exercise or thelevel of perceived stress during the color word test. Thisseems unlikely because both the workload during exerciseand the perception of stress during the color word test weresimilar in the diet plus exercise training and diet groups.

PerspectivesThe reduction in blood pressure and the restoration in muscleblood flow after diet plus exercise training have clinicalimplications. First, hypocaloric diet plus exercise trainingshould be the strategy of choice for treatment in children withobesity. Second, it is conceivable that the restoration in bloodpressure levels and muscle vasodilatation responses during

physiological maneuvers, achieved by this nonpharmacologi-cal treatment, prevents future cardiovascular disease inadulthood.

In conclusion, body weight loss by diet plus exercisetraining or diet alone prevents exaggerated blood pressureresponses during sustained static handgrip exercise and men-tal stress in obese children. In addition, diet plus exercisetraining, in contrast to diet alone, restores forearm vasodila-tation responses during these physiological maneuvers inobese children.

AcknowledgmentsThis study was supported by Fundação de Amparo à Pesquisa doEstado de São Paulo grant 1998/15983-8 and in part by FundaçãoZerbini.

References1. Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends

in overweight among US children and adolescents, 1999–2000. JAMA.2002;288:1728–1732.

2. Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL.Overweight prevalence and trends for children and adolescents: theNational Health and Nutrition Examination Surveys, 1963 to 1991. ArchPediatr Adolesc Med. 1995;149:1085–1091.

3. Negrão CE, Trombetta IC, Batalha LT, Ribeiro MM, Rondon MUPB,Tinucci T, Forjaz CLM, Barretto ACP, Halpern A, Villares SMF. Musclemetaboreflex control is diminished in normotensive obese women.Am J Physiol. 2001;281:H469–H475.

Figure 3. Mean blood pressure during static handgrip exerciseand mental stress in obese children subjected to a hypocaloricdiet or hypocaloric diet plus exercise training and in lean controlchildren. Note that mean blood pressure responses during bothstatic handgrip exercise and mental stress are similar amongthe 3 groups studied.

Figure 4. Forearm vascular conductance during static handgripexercise and mental stress in obese children subjected to ahypocaloric diet or hypocaloric diet plus exercise training and inlean control children. Note that forearm vascular conductanceresponses during both static handgrip exercise and mentalstress are similar between obese children subjected to hypoca-loric diet plus exercise training and lean control children. In con-trast, forearm vascular conductance responses during bothstatic handgrip exercise and mental stress were significantlyreduced in obese children subjected to a hypocaloric diet.†P�0.05 vs lean.




4. Kuniyoshi FH, Trobetta IC, Batalha LT, Rondon MU, Laterza MC,Gowdak MM, Barreto AC, Halpen A, Villares SM, Lima EG, Negrão CE.Abnormal neurovascular control during sympathoexcitation in obesity.Obes Res. 2003;11:1411–1419.

5. Trombetta IC, Batalha LT, Rondon UM, Laterza MC, Kuniyoshi FH,Gowdak MM, Barreto AC, Halpern A, Villares SM, Negrão CE. Weightloss improves neurovascular and muscle metaboreflex control in obesity.Am J Physiol. 2003;285:H974–H982.

6. Cole TJ, Bellizzi MC, Flegal KM, Deitz WM. Establishing a standarddefinition for child overweight and obesity worldwide: internationalsurvey. BMJ. 2000;320:1240–1243.

7. Cole TJ. The LMS method for constructing normalized growth standards.Eur J Clin Nutr. 1990;44:45–60.

8. Irace C, Ceravolo R, Notarangelo L, Crescenzo A, Ventura G, TamburriniO, Perticone F, Gnasso A. Comparison of endothelial function evaluatedby strain gauge plethysmography and brachial artery ultrasound. Athero-sclerosis. 2001;158:53–59.

9. Tulen JH, Moceman P, Van Steenis HG, Boomsma F. Characterization ofstress reactions to the Stroop color word test. Pharmacol Biochem Behav.1989;32:9–15.

10. Matthews DR, Hosker JP, Rudensky AS, Naylor BA, Treacher DF,Turner RC. Homeostasis model assessment: insulin resistance andbeta-cell function from fasting plasma glucose and insulin concentrationsin man. Diabetologia. 1985;28:412–419.

11. World Health Organization. WHO: Energy and protein requirements. In:Report of a Joint FAO/WHO/UNU Expert Consultation. Geneva, Swit-zerland: World Health Organization; 1985. Technical Report Series 724.

12. Wasserman K, Whipp BJ, Koyal SN, Beaver WL. Anaerobic thresholdand respiratory gas exchange during exercise. J Appl Physiol. 1973;33:236–243.

13. Wasserman K, Hansen JE, Sue DY, Whipp BJ. Measurement of thephysiological response to exercise. In: Wasserman K, Hansen JE, SueDY, Whipp BJ, eds. Principles of Exercise Testing and Interpretation.Philadelphia, Pa: Lea & Febiger; 1987:27–46.

14. Becque MD, Katch VL, Rocchini AP, Marks CR, Moorehead C.Coronary risk incidence of obese adolescents: reduction by exercise plusdiet intervention. Pediatrics. 1988;81:605–612.

15. National High Blood Pressure Education Program Working Group onHigh Blood. The fourth report on the diagnosis, evaluation, and treatmentof high blood pressure in children and adolescents. Pediatrics. 2004;114:555–576.

16. Ribeiro MM, Trombetta IC, Batalha LT, Rondon MUPB, Forjaz CLM,Barretto ACP, Villares SMF, Negrão CE. Muscle sympathetic nerveactivity and hemodynamic alterations in middle-aged obese women. BrazJ Med Biol Res. 2001;34:475–478.

17. Rocchini AP, Moorehead C, Katch V, Key J, Finta KM. Forearmresistance vessel abnormalities and insulin resistance in obese ado-lescents. Hypertension. 1992;19:615–620.

18. Woo KS, Chook P, Yu CW, Sung RYT, Qiao M, Leung SSF, Lam CWK,Metreweli C, Celermajer DS. Overweight in children is associated witharterial endothelial dysfunction and intima-media thickening. Int J ObesRelat Metab Disord. 2004;28:852–857.

19. Woo KS, Ping Chook, Yu CW, Sung RYT, Qiao M, Leung SSF, LamCWK, Metreweli C, Celermajer DS. Effects of diet and exercise onobesity-related vascular dysfunction in children. Circulation. 2004;109:1981–1986.

20. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N,Schuler G. Effect of exercise on coronary endothelial function in patientswith coronary artery disease. N Engl J Med. 2000;342:454–460.

21. Hambrecht R, Adams V, Gielen S, Linke A, Mobius-Winkler S, Yu J,Niebauer J, Jiang H, Fiehn E, Schuler G. Exercise intolerance in patientswith chronic heart failure and increased expression of inducible nitricoxide synthase in the skeletal muscle. J Am Coll Cardiol. 1999;33:174–179.

22. Paradis G, Lambert M, O’Loughlin J, Lavallée C, Aubin J, Delvin E,Lévy E, Hanley JÁ. Blood pressure and adiposity in children and ado-lescents. Circulation. 2004;110:1832–1838.

23. Knip M, Nuutinen O. Long-term effects of weight reduction on serumlipids and plasma insulin in obese children. Am J Clin Nutr. 1993;57:490–493.

24. Watts K, Beye P, Siafarikas A, Davis EA, Jones TW, O’Driscoll G, GreenDJ. Exercise training normalizes vascular dysfunction and improvescentral adiposity in obese adolescents. J Am Coll Cardiol. 2004;43:1823–1827.




Matos, Ivani C. Trombetta, Alfredo Halpern, Carlos E. Negrão and Sandra M.F. VillaresMaurício M. Ribeiro, Alexandre G. Silva, Nelson S. Santos, Isabel Guazzelle, Luciana N.J.

Physiological Maneuvers in Obese ChildrenDiet and Exercise Training Restore Blood Pressure and Vasodilatory Responses During

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