Haemodynamic Adjustments to Mental Stress in Normotensives and Subjects with Mildly Elevated Blood Pressure

Cardiac output, heart rate, stroke volume, pre-ejection period, total peripheral resistance, systolic and diastolic blood pressure, and oxygen consumption were monitored or derived in young men with mildly elevated casual blood pressures and unambiguously normotensive control subjects before, during, and after exposure to a mental arithmetic stress. Measurements were also taken while subjects underwent graded dynamic exercise. This permitted cardiac output-oxygen consumption regression equations to be calculated and, as a consequence, cardiac output during mental stress to be represented as additional cardiac output. Systolic and diastolic blood pressure were higher during all phases of the study in the mildly elevated blood pressure group. An overall groups effect during the mental stress phase of the experiment was observed for cardiac output and pre-ejection period, and the effect for stroke volume was close to significance. Significant Groups X Periods interactions were found for cardiac output and additional cardiac output, and the heart rate effect was nearly significant. Post-hoc comparisons here indicated that, in the main, group differences in these cardiac variables were more evident during the mental arithmetic stress than during the pre- and post-task baseline periods. Total peripheral resistance did not differ reliably between groups and the cardiac effects were specific to the mental stress phase of the study.     

Effect of Carotid Sinus Stimulation on Cardiac Output and Peripheral Vascular Resistance during Changes in Blood Volume Distribution in Man

In ten healthy subjects (mean age 29.6 years) the hemodynamic response to carotid sinus stimulation (neck suction - 40 mmHg) was studied under control conditions and during peripheral pooling of blood (lower body negative pressure). Heart rate, arterial and central venous pressure, cardiac output and forearm blood flow were measured. The time sequence of the heart rate response was studied separately in six healthy subjects. During control conditions, carotid sinus stimulation induced a significant decrease in arterial pressure and heart rate. The blood pressure decrease mainly reflected a reduction in cardiac output, total peripheral vascular resistance being essentially unchanged. However, in the skeletal muscle, represented by a forearm segment, vascular resistance decreased significantly. During lower body negative pressure (LBNP) the same stimulation of the carotid sinus induced a significantly greater fall in mean arterial pressure even though the reduction in cardiac output was slightly smaller on the average than in the control condition. The heart rate increased, probably secondary to a time dependent increase in heart rate elicited by the continuous LBNP stimulus. Total peripheral vascular resistance decreased significantly during LBNP, the reaction likewise differing significantly from that in the control condition. Thus the augmented blood pressure response was due to a more pronounced vasodilatation when the carotid sinus was stimulated during lower body negative pressure. The results indicate that the hemodynamic changes elicited by carotid sinus stimulation are modified by changes in the distribution of blood volume and in the tone of resistance vessels.     

Individual Differences in Behaviorally Evoked Cardiovascular Response: Temporal Stability and Hemodynamic Patterning

This study evaluates the reproducibility of individual differences in behaviorally evoked cardiovascular reactivity among 39 young adult males. Presented also are initial data describing idiosyncratic patterns of hemodynamic adjustment that may underlie pressor responses to laboratory stressors. Subjects were administered three experimental stressors (mental arithmetic, mirror tracing, and bicycle exercise) on two occasions, four weeks apart. Heart rate, blood pressure, and impedance-derived measurements of cardiac pre-ejection period, stroke index, cardiac index, and total peripheral resistance were obtained during baseline and task periods at each session. To index task-induced "reactivity," residualized (baseline-adjusted) change scores were calculated for all variables; percentage change from baseline was also calculated for impedance-derived hemodynamic measurements. Test-retest (inter-session) correlations were significant for nearly all baseline, task, and change-score measurements. The few exceptions included diastolic blood pressure changes during mirror tracing and bicycle exercise and changes in stroke index and peripheral resistance during mental arithmetic. Although virtually all baseline and task correlations exceeded .60, reactivity indices yielded consistently lower retest correlations (significant r's = .35-.78; median r = .49). In subsequent analyses, subsets of individuals were identified whose reactions to mental arithmetic at the first laboratory session reflected changes in either cardiac output (CI reactors, n = 9) or total peripheral resistance (TPR reactors, n = 6), or a combination of cardiac and vascular influences (Mixed reactors, n = 8). This typology of hemodynamic response: (a) was corroborated by corresponding group differences in heart rate, pre-ejection period, and stroke index; (b) was reproducible on retesting; and (c) showed some generalization to the mirror tracing task, though not to bicycle exercise.     

Blood pressure regulation IV: adaptive responses to weightlessness

During weightlessness, blood and fluids are immediately shifted from the lower to the upper body segments, and within the initial 2 weeks of spaceflight, brachial diastolic arterial pressure is reduced by 5 mmHg and even more so by some 10 mmHg from the first to the sixth month of flight. Blood pressure thus adapts in space to a level very similar to that of being supine on the ground. At the same time, stroke volume and cardiac output are increased and systemic vascular resistance decreased, whereas sympathetic nerve activity is kept surprisingly high and similar to when ground-based upright seated. This was not predicted from simulation models and indicates that dilatation of the arteriolar resistance vessels is caused by mechanisms other than a baroreflex-induced decrease in sympathetic nervous activity. Results of baroreflex studies in space indicate that compared to being ground-based supine, the carotid (vagal)-cardiac interaction is reduced and sympathetic nerve activity, heart rate and systemic vascular resistance response more pronounced during baroreflex inhibition by lower body negative pressure. The future challenge is to identify which spaceflight mechanism induces peripheral arteriolar dilatation, which could explain the decrease in blood pressure, the high sympathetic nerve activity and associated cardiovascular changes. It is also a challenge to determine the cardiovascular risk profile of astronauts during future long-duration deep space missions.     

Behaviorally-evoked plasma catecholamine response and 24-hour excretion of urinary catecholamines among cardiac and vascular reactors

Individuals differ in the cardiac and vascular processes that underlie blood pressure elevations evoked by environmental stimuli; such differences may reflect variability in sympathoadrenal response. We separated 108 healthy, young-adult males into those with predominant elevations in either cardiac output or peripheral resistance when exposed to psychological challenges. We then asked if they differed on other measures of cardiovascular response, concomitant plasma catecholamine reactions or 24-h urinary excretion of catecholamines. Cardiac reactors, relative to vascular reactors, showed reduced cardiac pre-ejection period, a smaller reduction in stroke volume, and elevated plasma epinephrine response and 24-h urinary epinephrine excretion. Vascular reactors, relative to cardiac reactors, responded to mental stress with more elevated diastolic blood pressure, a rise in peripheral resistance and pulse wave velocity, and a greater reduction in stroke volume. Vascular reactors, however, did not show plasma norepinephrine response or 24-h urinary norepinephrine excretion that was greater than cardiac reactors. The results provide partial support for the hypothesis that variability in sympathoadrenal activity contributes to individual differences in cardiac and vascular reactivity, and extend prior observations by demonstrating covariation of behaviorally-elicited cardiac reactivity with the 24-h excretion of epinephrine.     

Circulatory effects of noise

Thirteen patients with mild essential hypertension, mean age 44 years (range 21-59), were studied during "stress" before and after postsynaptic alpha-adrenoceptor blockade and combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade. Loud broad band noise (100 dBA for 10 min) was used as the stress stimulus. Exposure to noise caused a significant increase in systolic (7%, p less than 0.05), diastolic (9%, p less than 0.01) and mean arterial pressure (6%, p less than 0.01). The blood pressure elevation was caused by an increase in total peripheral resistance (12%, p less than 0.05). There was no significant change in heart rate, stroke volume or cardiac output. The blood pressure response during noise stimulation was not affected by postsynaptic alpha-adrenoceptor blockade (prazosin, 2 mg orally). The hemodynamic reaction pattern, however, was totally reversed. Thus, the cardiac output increased significantly (9%, p less than 0.05), while the total peripheral resistance tended to decrease. Combined postsynaptic alpha- and non-selective beta-adrenoceptor blockade (labetalol, 200 mg orally) inhibited the increase in systolic blood pressure caused by noise, while the diastolic and mean arterial pressures still increased significantly (5%, p less than 0.01). Labetalol effectively blocked the stress-induced increase in total peripheral resistance and there was no significant increase in cardiac output after combined alpha- and beta-adrenoceptor blockade. Exposure to noise caused a significant increase in circulating noradrenaline (20%, p less than 0.05). Plasma adrenaline and plasma renin activity were not affected by noise stimulation. These results suggest that blood pressure elevation is essential during "stress" but that the hemodynamic pattern causing blood pressure elevation may vary and may be affected by pharmacological blockade of various parts of the sympathetic nervous system.     

Cardiovascular dynamics in blood phobia: evidence for a key role of sympathetic activity in vulnerability to syncope

This study was aimed at clarifying the mechanism predisposing people with blood phobia to syncope by investigating the complete hemodynamic response pattern and the underlying autonomic control. Blood phobics and controls were shown 3 film-clips: phobia-related, phobia-unrelated, and neutral. Hemodynamic responses were recorded using impedance cardiography and Finapres. Preejection period and respiratory sinus arrhythmia were employed as indices of cardiac sympathetic and parasympathetic activity. Self-ratings of emotion were also collected. Blood phobics displayed global heart rate and cardiac output increases to the phobic film, mediated by augmented cardiac sympathetic activity. Systolic blood pressure and total peripheral resistance markedly declined, with no evidence of diphasic reaction or parasympathetic activation. An impaired vasomotor response under sympathetic control might be the key mechanism underlying the phobic dysfunctional response.     

Influence of Age on Sensitivity and Effector Mechanisms of the Carotid Baroreflex

In 30 healthy subjects aged 20–48 years the hemodynamic response to carotid sinus stimulation (neck suction -40 mmHg) was studied. Heart rate, arterial pressure and cardiac output (dye dilution technique) were measured. In order to evaluate the effect of age on carotid sinus function the material was subdivided into two arbitrary subgroups, aged up to 30 years (n = 15) respectively 30 years and above (n = 15). Carotid sinus stimulation induced a significantly greater reduction in mean arterial pressure in the younger group compared to the older group. The heart rate reduction was, on the average, slightly greater in the younger group though the difference was not significant. In both groups a significant decrease in cardiac output contributed to the demonstrated reduction in mean arterial pressure. As the decrease in cardiac output was, on the average, slightly smaller in the younger group, the results indicate that the greater blood pressure response in the younger group was due to a greater reduction in peripheral vascular resistance. This is further supported by the finding of a significant correlation between changes in total peripheral vascular resistance, elicited by carotid sinus stimulation and age.     

Regulation of cardiac function during a cold pressor test in athletes and untrained subjects

By using (dP/dt)/P of carotid artery pulse, a non-invasive index of cardiac contractility, we examined the regulatory mechanism of cardiac function during a cold pressor test in athletes and untrained subjects. Twenty-four healthy subjects (9 athletes, 8 untrained subjects, and 7 hyperreactors of 4 athletes and 3 untrained subjects with a rise of 15 mmHg or greater in systolic and/or diastolic blood pressure) underwent the cold pressor test according to Hines and Brown (Am Heart J 11:1–9, 1936): immersion of the right hand in 4°C water for 1 min. Although mean blood pressure increased during the cold stress in all the groups, cardiac function differed. In athletes, heart rate and cardiac contractility caused cardiac output to increase while total peripheral resistance (TPR) did not change. In untrained subjects, however, heart rate and cardiac contractility tended to decrease cardiac output and thus TPR increased. In hyperreactors, heart rate and cardiac contractility increased during cold stress, and also TPR increased. After the end of the test, heart rate and cardiac contractility decreased only in untrained group. The findings that during a cold pressor test heart rate and cardiac contractility are enhanced in athletes but depressed in untrained subjects indicate that the state of physical training influences cardiac sympathetic neural reactivity to cold stress, except for hyperreactors.     

Effects of stress management on blood pressure and other cardiovascular variables.

Blood pressure and impedance cardiography derived measures of heart rate, stroke volume, cardiac output and total peripheral resistance were measured in 16 persons before and after participation in a comprehensive program of stress management that included home monitoring of blood pressure and feedback of finger skin temperature during relaxation. Ten of the subjects were hypertensive and six were normotensive. Baseline measures of systolic and diastolic blood pressure and heart rate decreased significantly after participation in the program. In addition, reactivity to a psychological stressor (oral quiz) was significantly lower as revealed in reduced systolic and diastolic pressure, heart rate and cardiac output at the second assessment. A reduction in sympathetic nervous system activity is postulated as a possible mechanism for the changes observed.     

Electrodermal Lability and Myocardial Reactivity to Stress

The relationship between electrodermal lability and myocardial reactivity to stress was examined in male undergraduates, who were classified as electrodermally labile (n = 19) or stabile (n = 19) based on the frequency of nonspecific skin conductance responses at rest. Heart rate, pre-ejection period, cardiac output, and skin conductance responses were recorded at rest, during task instructions, and during two mental arithmetic tasks that varied in level of difficulty. As predicted, labiles exhibited greater myocardial reactivity to the task instructions and the tasks than did stabiles, with more persistent group differences emerging for pre-ejection period and cardiac output than for heart rate. The group differences did not vary as a function of task difficulty, but did decline over time. These results support a positive relationship between electrodermal lability and beta-adrenergic myocardial reactivity to stress, particularly under conditions of task novelty or uncertainty, and suggest that electrodermal lability is related fundamentally to arousal and reactivity processes.     

Cardiovascular Reactivity During Positive and Negative Marital Interactions

Marriage reduces risk of cardiovascular disease (CVD) but marital stress increases risk, perhaps through cardiovascular reactivity (CVR). However, previous studies have lacked controls necessary to conclude definitively that negative marital interactions evoke heightened CVR. To test the specific effects of marital stress on CVR, 114 couples engaged in positive, neutral, or negative interactions in which speaking and task involvement were controlled. Compared to positive and neutral conditions, negative discussions evoked larger increases in systolic blood pressure, heart rate, and cardiac output, and larger decreases in peripheral resistance and pre-ejection period--similarly for men and women. Hence, CVR could contribute to the effects of marital difficulties on CVD. Previous evidence of sex differences in this effect might reflect factors other than simple reactivity to negative interactions.     

Pathogenesis and etiology of essential hypertension: role of dietary carbohydrate

The development of essential hypertension (EH) is proposed to be the result of a cascade of metabolic alterations, with high insulin levels/hyperinsulinemia and an abnormal reaction to the vasodilatory effect of insulin as the initiating factors. It is well established that insulin causes vasodilatation of peripheral resistance vessels. In normal subjects, this insulin-induced vasodilatation and decrease of the peripheral vascular resistance (PVR) is compensated by an SNS-mediated re-vasoconstriction in order to avoid hypotension, with the net effect of a slight decrease in blood pressure and no significant effect on peripheral vascular resistance. In contrast, in genetically predisposed subjects, prone to the development of essential hypertension, the insulin-induced vasodilatation is compensated by an increased heart rate and cardiac output (to avoid hypotension), mediated by an abnormal sympathetic overactivity, (characterised by high norepinephrine spillover rates and (frequently) a hyperdynamic circulation), while the PVR remains low during the early phase of developing EH. During the course of chronic hypertension, the SNS-overactivity leads to progressive trophic alterations of vessel walls, and structural and functional vascular remodeling, with narrowing of arterial resistance vessels and an increasing PVR. Vascular remodeling and lumen narrowing not only affect peripheral resistance vessels, but also kidney vessels. Narrowing and decreased distensibility of preglomerular kidney vessels lead to chronic activation of the Renin-Angiotensin-Aldosterone-System, with reinforcement and fixation of hypertension. High-glycemic index nutrition is suggested to play a key role in the etiology of hypertension: The chronic stimulus of pancreatic beta-cells due to high-glycemic index nutrition may cause cell hypertrophy and dysfunction, resulting in postprandial hyperinsulinemia, and -- in susceptible subjects -- the development of EH. Since significant evidence suggests that hyperinsulinemia also represents a key factor for the development of obesity, insulin resistance and the metabolic syndrome, the well-known common association of EH and these metabolic alterations becomes quite understandable.     

Effect of gastric distension on cardiovascular parameters: gastrovascular reflex is attenuated in the elderly

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 ± 3.2 years, mean ± s.e.m. ) and eight healthy elderly subjects (7 men and 1 woman, 76 ± 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group ( P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects ( P < 0.01). The older group tended to show a higher increase in mean arterial pressure ( P = 0.08), heart rate ( P = 0.06) and total peripheral arterial resistance ( P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.     

Cardiovascular 'reactivity' to graded splanchnic nerve stimulation in spontaneously hypertensive and normotensive control rats.

Cardiovascular 'reactivity' to graded splanchnic nerve stimulation was compared in adult spontaneously hypertensive rats (SHR) and normotensive controls (NCR), during abolished adrenal medullary secretion and neurogenic cardiac control and depressed reflex vascular adjustments. Arterial pressure, heart rate and cardiac output were measured, and total peripheral resistance (TPR) and stroke volume (SV) computed before, during and after nerve stimulation. The neurogenic resistance increases in the major gastrointestinal-renal-hepatic circuits expressed themselves as TPR elevations, which were much accentuated in SHR. This reflects an increased w/ri of SHR resistance vessels rather than any altered effector sensitivity, since the responses were particularly accentuated at high discharge rates when noradrenaline junction concentrations approach maximal levels. The splanchnic capacitance responses expressed themselves as SV increases, being the most relevant aspect of capacitance control. SV increased less in SHR, mainly reflecting the reduced diastolic compliance of the hypertrophied SHR left ventricle and the consequent rightward shift of its Frank-Starling curve. The results indicate that an elevated resistance may well be maintained by a normal sympathetic discharge in established SHR hypertension. There seems, however, to be an increasing need for accentuated discharge to the capacitance side to maintain proper cardiac filling of the hypertrophied left ventricle.     

Changes in regional blood flow and cardiodynamics evoked by electrical stimulation of the fastigial nucleus in the cat and their similarity to orthostatic reflexes

1. Changes in regional blood flow and cardiodynamics were measured in anaesthetized paralysed cats during electrical stimulation of the rostral fastigial nucleus.2. Fastigial stimulation results in a graded, highly reproducible and stereotyped cardiovascular response characterized by (a) increased systolic, diastolic and mean arterial pressures without changes in central venous or occluded vein pressure, (b) decreased blood flow and increased vascular resistance in the axillary, renal, femoral and mesenteric arteries, increased flow without any change in vascular resistance in the common carotid artery, and increase in total peripheral resistance, (c) a small increase in heart rate and myocardial contractile force, decrease in calculated stroke volume, and no change in the cardiac output.3. Changes in regional arterial flow were abolished by transection of sympathetic nerves or blockade of alpha-adrenergic receptors by systemic administration of phentolamine.4. Changes in heart rate and myocardial contractility were abolished by stellate ganglionectomy or blockade of beta-adrenergic receptors by propranolol.5. No changes in pupillary diameter or retraction of the nictitating membrane were seen during fastigial stimulation with stimuli producing substantial changes in blood pressure.6. The fastigial pressor response represents a highly reproducible, stereotyped, graded, and differentiated pattern of activation of sympathetic preganglionic neurones.7. The pattern of cardiovascular effects of fastigial stimulation simulates the compensatory (orthostatic) reflex response to maintenance of an upright posture.8. Fastigial stimulation appears to excite the neural network subserving orthostatic reflexes.     

The Effect of Overweight/Obesity on Cardiovascular Responses to Acute Psychological Stress in Men Aged 50-70 Years

BackgroundTo determine the effect of adiposity in males aged 50-70 years on cardiovascular responses to acute psychological stress.MethodsLean (BMI 20-25 kg/m²) (n = 21) and overweight/obese (BMI 27-35 kg/m²) (n = 21) men aged 50-70 years were subjected to psychological stress. Systolic blood pressure, diastolic blood pressure, heart rate, total peripheral resistance, and cardiac output were measured by a Finometer during resting (60 min), stress (30 min), and recovery (90 min).ResultsThe lean group had a significantly higher SBP stress reactivity when compared to the overweight/obese group (51.5 ± 3.7% vs. 41.0 ± 2.9% (mean ± SEM); p < 0.05). A significant effect of time was observed for systolic blood pressure, diastolic blood pressure, heart rate, total peripheral resistance, and cardiac output (p < 0.0001 for all). There were significant time × body type interactions for systolic blood pressure, diastolic blood pressure, heart rate, total peripheral resistance, and cardiac output (p < 0.05 for all). Total peripheral resistance during recovery was higher in the lean compared to the overweight/obese group (p < 0.05). In the lean group, systolic and diastolic blood pressure variability remained elevated after stress (p < 0.05) but returned to resting levels in the overweight/obese group (p > 0.05).ConclusionModerate adiposity in men was associated with reduced systolic blood pressure % reactivity, total peripheral resistance, and blood pressure variability after psychological stress. Overweight/obese men appear to be at no greater risk of unfavorable cardiovascular responses to stress.Key Words: Stress, Blood pressure, Obesity, Adults     

Hemodynamic determinants of chronic hypotension and their modification through vasopressor application

Chronic low blood pressure is typically accompanied by symptoms such as fatigue, reduced drive, dizziness, headaches and cold limbs. Reduced cognitive performance, diminished cerebral blood flow and autonomic dysregulation have been furthermore documented in this condition. The present contribution reports two studies exploring systemic hemodynamics in chronic hypotension and their modification through vasopressor application. In study I, effects of the alpha-sympathomimetic midodrine were examined in 54 hypotensive individuals using a placebo-controlled double-blind design. Hemodynamic parameters were assessed at rest and during mental stress. They were derived from continuous blood pressure recordings using Modelflow analysis. The drug led to marked increases in blood pressure, total peripheral resistance and stroke volume. However, due to strong heart rate deceleration, cardiac output remained virtually unchanged. In study II, 40 hypotensive and 40 normotensive control persons were compared with respect to hemodynamics. While groups did not differ in total peripheral resistance, hypotensives exhibited markedly diminished stroke volume and heart rate, resulting in a reduction in cardiac output of 25% at rest and of 33% during mental stress. The data provide relevant knowledge about the hemodynamic mediation of chronic hypotension. In contrast to elevated blood pressure, which is mainly determined by increased peripheral resistance, reduced cardiac output may be the cardinal hemodynamic aberration in chronic hypotension. Midodrine proved to be effective in elevating blood pressure. However, given the cardiac origin of chronic hypotension and the lack of drug effect on cardiac output, alpha-sympathomimetic treatment may be suboptimal.     

Cardiovascular reactivity, Type A behavior, and coronary heart disease: Comparisons between myocardial infarction patients and controls during laboratory-induced stress

Cardiovascular responses to a series of laboratory stressors were examined in middle-aged Type A and Type B men. The subjects were 30 patients with diagnosed myocardial infarction (NYHA Class 1) and 26 age-matched healthy controls. All subjects were nonsmokers in the normotensive range, and none were on medication. Blood pressure, heart rate, forearm blood flow and resistance, and impedance cardiography-determined response variables were obtained during performance and recovery periods of both mental and physical tasks. The patients showed elevated reactivity in systolic blood pressure and cardiac output and prolonged systolic lime ratio during mental stress tasks and elevated total peripheral resistance and lower cardiac output and stroke volume during physical tasks, as compared with control subjects. Thus, the difference in blood pressure reactivity between patients and controls appeared to be primarily dependent on the vascular component during physical tasks, whereas the mental tasks promoted a hemodynamic response pattern more consistent with beta adrenergic activation. Type A men, irrespective of coronary status, showed larger systolic and diastolic blood pressure response to both mental and physical stress than did Type B men.     

Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome

The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS. We included a consecutive sample of 15 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls. During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls. Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction.