Do elderly patients with an excessive fall in blood pressure on standing have evidence of autonomic failure?

1. Blood pressure, heart rate and plasma catecholamine responses were examined in two groups of elderly subjects distinguished by blood pressure responses to standing. Subjects in the control group showed a fall of less than 15 mmHg in systolic blood pressure on standing; subjects in the orthostatic hypotension group had falls of more than 20 mmHg systolic and 10 mmHg diastolic blood pressure on standing. 2. The heart pressure response on standing showed no significant difference between the two groups. 3. The orthostatic hypotension patients had lower plasma noradrenaline concentrations than the control patients (P less than 0.01) in the supine position, but during 10 min standing there was no significant difference in noradrenaline levels between the groups, and the percentage increase of noradrenaline levels in the orthostatic hypotension group was greater (P less than 0.05) than in the control group. 4. In the supine position, diastolic blood pressure was higher (P less than 0.05) in the orthostatic hypotension group than in the control group. 5. We conclude that impairment of baroreceptor function is not involved in most cases of orthostatic hypotension in the elderly, nor is there reduction of sympathetic nervous activity. We suggest that mechanical changes or adrenoreceptor dysfunction are more likely to be important factors in orthostatic hypotension in the elderly.     

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.     

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma adrenaline and noradrenaline during orthostasis in man: the importance of arterial sampling

Plasma adrenaline and noradrenaline were measured in arterial blood and in forearm venous blood during supine rest and after 30 min standing in normotensive, healthy 50-year-old men (n = 16). After 30 min standing, venous noradrenaline had increased from 1.61 +/- 0.11 to 4.22 +/- 0.30 nmol/l and arterial from 1.43 +/- 0.06 to 2.93 +/- 0.15 nmol/l. Orthostasis induced a seven-fold increment in the forearm arterial-venous difference of noradrenaline from -0.18 +/- 0.08 to -1.29 +/- 0.25 nmol/l (p less than 0.001). Orthostasis more than doubled the forearm arterial-venous difference of adrenaline from 0.15 +/- 0.03 to 0.31 +/- 0.05 nmol/l (p less than 0.001) since arterial adrenaline increased from 0.31 +/- 0.03 to 0.53 +/- 0.05 nmol/l and venous from 0.16 +/- 0.02 to 0.22 +/- 0.02 nmol/l. Arterial adrenaline correlated significantly with venous in the supine (r = 0.64, p less than 0.01) but not in the standing position (r = 0.34, NS). The results indicate that arterial concentrations of adrenaline are a much better indicator of sympatho-adrenal activity during orthostasis than peripheral venous concentrations. For noradrenaline, measurements of arterial concentrations during the orthostatic manoeuvre seem to provide information about the total noradrenergic sympathetic reactivity, while the corresponding measurements in peripheral venous blood represent the forearm locally.     

Hypotension induced by central hypovolaemia and hypoxaemia

Summary. Our question was whether the reduced orthostatic tolerance that accompanies hypoxaemia in some (not all) subjects might be associated with an abnormally large release of adrenaline. Eight normal young men were exposed to lower body negative pressure (LBNP) at —30 to —40 mmHg while breathing air or 10% O₂ in N₂. Four subjects developed hypotension and bradycardia whenever LBNP was applied during hypoxaemia; four showed a rise in heart rate and stable blood pressure. During normoxia plasma adrenaline concentration did not rise during LBNP in any subject, nor during hypoxaemia plus LBNP in the subjects who remained normotensive. In the four men whose heart rates and blood pressures fell during LBNP with hypoxaemia, adrenaline rose markedly, reaching 200–1600 pg ml^-1. All subjects showed similar elevations in noradrenaline concentration during LBNP in both normoxia and hypoxaemia. The results suggest that reduced tolerance to central hypovolaemia during hypoxaemia could stem from known vasomotor and cardiac effects attending high plasma concentrations of adrenaline.     

Cardiovascular properties of metkephamid, a delta opioid receptor agonist, in man

Opioid receptors exist in at least three forms: mu, delta and kappa. Agonists at mu receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective delta opioid receptor agonist. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70 degrees 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration. We conclude that delta as well as mu opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with mu receptor agonists, suggesting a possible role of delta opioid receptors in cholinergic activity.     

Venous plasma adrenaline response to orthostatic syncope during tilting in healthy men

Summary. The effect of transient cerebral ischaemia connected with acute orthostatic hypotension on plasma adrenaline and noradrenaline levels was studied in seven healthy male volunteers during tilt. Sublingual administration of 1 mg nitroglycerin was used to block peripheral vascular reflexes and thus to provoke orthostatic intolerance. A consistent increase in plasma adrenaline concentrations (from 19·2 to 104·3 pg/ml on average, P<0·01) was found in six subjects who developed clinical signs of collapse after tilting. Plasma adrenaline never changed after tilting without collapse. Posturally stimulated plasma noradrenaline increases were similar yet irrespective of the presence of collapse.     

Adrenergic supersensitivity in Parkinsonians with orthostatic hypotension

The adrenergic status was studied through evaluation of platelet alpha 2-adrenoceptor number [( 3H]yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P less than 0.05) decreased from 144 +/- 9 and 76 +/- 6 mmHg in the lying position to 95 +/- 12 and 60 +/- 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 +/- 11 pg ml-1, (P less than 0.05) when compared with controls (219 +/- 13 pg ml-1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 +/- 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P less than 0.01) lower in Parkinsonians with orthostatic hypotension (0.19 +/- 0.03 microgram kg-1) when compared with Parkinsonians without orthostatic hypotension (0.86 +/- 0.11 microgram kg-1) or with controls (0.68 +/- 0.1 microgram kg-1). Platelet alpha 2-adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 +/- 52 fmol mg-1 protein) than in Parkinsonians without orthostatic hypotension (168 +/- 9 fmol mg-1 protein) or in controls (175 +/- 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet alpha 2-adrenoceptor number.(ABSTRACT TRUNCATED AT 250 WORDS)     

Orthostatic circulatory control in the elderly evaluated by non-invasive continuous blood pressure measurement

1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age. 2. During the first 30 s (initial phase) the effects of active standing and passive head-up tilt closely resembled those observed earlier in younger age groups. Standing up was accompanied by a drop (mean +/- SD) in systolic and diastolic blood pressures of 26 +/- 13 mmHg and 12 +/- 18 mmHg, respectively, at around 10 s, and a subsequent rise up to 11 +/- 17 mmHg and 8 +/- 6 mmHg above supine values at around 20 s. The drop in blood pressure upon standing was accompanied by a transient increase in heart rate with a maximum of 13 beats/min, followed by a gradual decrease to 7 beats/min above supine levels. These characteristic transient changes were absent upon a passive head-up tilt. 3. After 1-2 min of standing (early steady-state phase) diastolic blood pressure and heart rate increased significantly after active and passive postural changes. On average, for all subjects systolic blood pressure tended to increase from control during 5-10 min standing, reaching a significant difference at 10 min. During standing, the largest increases in systolic blood pressure were found in subjects with the lowest supine blood pressures. 4. In conclusion, for the investigation of orthostatic circulatory responses in elderly subjects the following factors have to be taken into account: active versus passive changes in posture, the timing of the blood pressure reading, and the level of supine blood pressure.     

Effects of yohimbine, an α2-adrenoceptor antagonist, on experimental neurogenic orthostatic hypotension

Summary— Yohimbine has been proposed for the treatment of neurogenic orthostatic hypotension; however, no controlled trial has been performed in experimental models of orthostatic hypotension or in patients with autonomic failure. The aim of the present study was to compare the effects of yohimbine (0.05 mg/kg, intravenously [iv]) and placebo (saline) in a new model of neurogenic orthostatic hypotension obtained by sinoaortic denervation (SAD) in chloralose-anaesthetized dogs. Blood pressure, heart rate, noradrenaline plasma levels and systolic blood pressure and heart rate short-term variabilities (calculated on low frequency [40–50 MHz] and high frequency [390–490 MHz] bands) were measured in supine position and after a 10 min 80° head-up tilting. The drugs were administered in a double-blind cross-over randomized fashion. The head-up tilting performed in normal animals increased diastolic blood pressure (+12 ± 4 mmHg), heart rate (+39 ± 12 beats per minute [bpm]), the low frequency band of systolic blood pressure and noradrenaline plasma level, without changing systolic blood pressure or heart rate variability. In SAD dogs, a marked fall in systolic (-80 ± 11 mmHg) and diastolic (-43 ± 4 mmHg) blood pressures was observed within 1 min after placebo, without modification in heart rate, systolic blood pressure and heart rate short-term variabilities and noradrenaline plasma levels. In SAD dogs, yohimbine (0.05 mg/kg, iv) delayed the blood pressure fall elicited by head-up tilting, but failed to modify its magnitude. These results show that, in the model of orthostatic hypotension obtained by SAD, yohimbine, at an α₂-adrenoceptor selective dose (0.05 mg/kg), delays the fall in blood pressure elicited by head-up tilting. The effect of yohimbine can be explained by an increase in sympathetic tone.     

Why does vasodilatation occur during syncope?

1. Syncopal or near syncopal episodes have been observed in five subjects who stood or were tilted and in whom blood samples were being taken. 2. In all subjects bradycardia and hypotension developed before the onset of symptoms. Increases in plasma adrenaline concentrations occurred in all subjects, beginning before the faint. Changes in plasma noradrenaline concentrations were variable: in three subjects there was a marked fall and in the other two subjects an increase. Plasma vasopressin increased in all subjects. 3. Increase in plasma adrenaline may be contributing to the vasodilatation and arterial hypotension which occur during syncope.     

Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.     

Effects of tilting in the anaesthetized and mechanically ventilated rat: a model of orthostatic hypotension

The main of the present study was to determine the experimental conditions for an animal model of orthostatic hypotension based on tilting in rats. Blood pressure, heart rate and plasma catecholamine levels were measured before and after tilting in conscious and anaesthetized rats either breathing spontaneously or mechanically ventilated. In conscious rats, tilting did not alter arterial blood pressure, but increased heart rate and plasma catecholamine levels. In anaesthetized rats, tilting induced a drop in arterial blood pressure without any modification in plasma catecholamine concentrations. Mechanical ventilation significantly increased the postural hypotension and the percentage of rats showing a decrease in heart rate. Tyramine infusion increased plasma noradrenaline levels, and reduced or counteracted the postural hypotension and bradycardia. The results show that anaesthetized mechanically ventilated rats might constitute an appropriate model of orthostatic hypotension.     

Intra-individual variability in postural blood pressure in the elderly

Orthostatic hypotension, an age-related phenomenon, has been associated with hypertension and body weight variability. To evaluate the relative contributions of blood pressure elevation and abnormalities in extracellular volume regulation to orthostatic hypotension, elderly institutionalized subjects (mean age = 87 +/- 7 years), taking no cardiovascular medications, underwent measurement of body weight (n = 15) and first morning supine and standing blood pressures (n = 19), 12-13 times per subject over a 2-4 week period. There was a wide day-to-day variability in postural systolic blood pressure change (coefficient of variation = 533%) and a strong negative correlation between each day's postural change in systolic blood pressure and basal supine blood pressure (r = -0.55, P less than 0.0001). There was no association between postural blood pressure change and heart rate response or body weight changes, which were very small over the duration of the study (coefficient of variation = 0.6%). Elderly individuals have intact homeostatic mechanisms for the control of standing pressure when basal blood pressure is normal. Postural hypotension in the elderly is a variable phenomenon related to elevations in basal blood pressure.     

Cardiovascular control and plasma catecholamines during rest and mental stress: effects of posture.

In order to understand the complex autonomic adjustments that occur during the psychological challenges of normal daily life, autonomic responses to psychological stress were studied by evaluating the effects of body posture on various indices of sympathetic and parasympathetic regulation during performance of a psychological task. Twelve male subjects were studied in various postures (supine, sitting and standing), and during performance of the Colour Word Test (CWT) when sitting and then when standing. This procedure was subsequently repeated in reverse order (first standing and then sitting) after 15 min of supine rest. Blood samples for assay of plasma catecholamines were obtained before and during each CWT. Spectral analysis of beat-to-beat variations of heart rate (HR) and blood pressure (BP) was applied in order to obtain non-invasive indices of sympathetic and parasympathetic regulation. HR, diastolic BP, mid-frequency band power (0.07-0.14 Hz) of HR and systolic BP, and plasma adrenaline and noradrenaline concentrations showed significant increases when changing from supine to sitting to standing posture, whereas high-frequency band power (0.15-0.50 Hz) of HR decreased in a posture-dependent fashion. In the sitting position, the CWT caused significant increases in HR, BP and plasma adrenaline levels, and decreased HR and BP variability indices. In the standing posture, the CWT responses differed significantly from those during sitting for HR (a mild decrease during standing), high-frequency band power of HR (decreased more while sitting), high-frequency band power of BP (decreased more while standing), and plasma adrenaline responses (larger during sitting). Posture-related differential effects were observed on indices of sympatho-adrenomedullary activation during performance of a psychological challenge, whereas indices of parasympathetic activity indicated primarily less vagolytic effects when the task was performed in the standing posture. Our findings therefore underline the complexity of the adjustments that occur in neurohumoral and haemodynamic parameters during the psychological challenges of daily life.     

Changes in plasma free 3,4-dihydroxyphenylethylene glycol and noradrenaline levels after acute alcohol administration

The effects of alcohol (0.9 g/kg) compared with placebo (400 ml of orange juice) on plasma noradrenaline and 3,4-dihydroxyphenylethylene glycol levels, and on erect and supine blood pressures and heart rates, were studied in eight normal male volunteers. Alcohol caused a rise in noradrenaline levels that commenced approximately 30 min after drinking and lasted about 4 h. In contrast, 3,4-dihydroxyphenylethylene glycol levels fell immediately after alcohol administration and remained low for at least 6 h. Acute alcohol administration alters noradrenaline catabolism, and may have a dual effect of increasing noradrenaline release and decreasing noradrenaline clearance. Alcohol caused a transient rise in erect and supine blood pressures that preceded the rise in plasma noradrenaline. Thereafter erect blood pressures fell compared with control. This fall was associated with a progressive rise in both supine and erect rates, and reached a maximum several hours after the maximum levels of blood alcohol. The major effect of acute alcohol administration is to lower blood pressure and induce a reflex tachycardia. Changes in noradrenaline and 3,4-dihydroxyphenylethylene glycol levels did not readily explain changes in blood pressure or heart rate, suggesting that alcohol induced changes in noradrenaline metabolism occur largely independent of changes in blood pressure and heart rate.     

Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion.

In contrast to the tachycardia and unchanged or increased blood pressure seen after single doses, prolonged delta-9-tetrahydrocannabinol (THC) ingestion produced significant heart rate slowing and blood pressure lowering in hospitalized volunteers. Impaired circulatory responses to standing, exercise, Valsalva maneuver, and cold pressor testing suggest a state of sympathetic insufficiency. Marked weight gain was observed in all subjects, which has been shown to be related to fluid retention and plasma volume expansion. Tolerance developed to orthostatic hypotension, possibly related to plasma volume expansion, but did not develop to the supine hypotensive effects. Nearly complete tolerance developed to the tachycardia and psychological effects produced by smoked marijuana while ingesting THC. Electrocardiographic changes were minimal despite the large cumulative dose of THC. The hypothesis that THC has a biphasic effect on the sympathetic nervous system in man, producing excitation with single doses and inhibition with prolonged administration, is discussed.     

Effect of changes in posture on circulatory homeostasis in patients with the nephrotic syndrome

Summary. To assess whether the upright posture causes circulatory hypovolaemia in patients with the nephrotic syndrome (NS), we studied 12 subjects with NS and 12 healthy subjects during recumbency, 110 min of standing, followed again by recumbency. Control blood-pressure was 134/88±4/3 mmHg in the patients and 113/75±2/3 mmHg in the normal subjects (P<0.01), and remained higher in the patients throughout the procedure. Heart rate was continuously higher in the patients (P<0.05), but acceleration on standing was normal. The blood volume, which was not different during recumbency, had fallen below that in normal subjects after 25 min of standing (P<0.05), due to excessive plasma volume reduction (-16.8±0–8% in the patients against -11.7±1.2% in the normals, P<0.02). Plasma renin activity (PRA) was higher in the patients while recumbent (P<0.001) but not during standing, due to a blunted response in some. No significant differences in plasma noradrenaline were found, but four patients reacted with an excessive rise in plasma noradrenaline and heart rate. This subset, which had high PRA levels as well, comprised the only subject who experienced orthostatic hypotension. It is concluded that during standing an excessive drop in plasma volume leads to a lowered blood volume in NS patients. This forms a paradox with the heart rate acceleration and noradrenaline levels, which were mostly normal, and with the blood-pressure, which remained slightly elevated. Even in a few patients with enhanced stimulation of heart rate and noradrenaline, blood-pressure was found to be high in the majority of cases. PRA was usually found to be increased but, in part, independent of posture.     

Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise

1. Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.     

Increased plasma noradrenaline and serum gastrin in patients with duodenal ulcer

Serum gastrin, serum insulin, plasma noradrenaline, plasma adrenaline, pulse rate and blood pressure were measured repeatedly during 24h in six patients with duodenal ulcer and in six control subjects. Mean serum gastrin concentration was 3-4 times higher in duodenal ulcer patients than in controls during both the day and at night. Serum insulin was the same in both groups of subjects. Overnight fasting and mean supine plasma noradrenaline as well as mean supine pulse rate were significantly higher in duodenal ulcer patients than in controls. Plasma adrenaline and arterial blood pressure were the same in patients and controls. These results suggest that sympathetic nervous activity is increased in patients with duodenal ulcer. The increased sympathetic nervous activity may mean that duodenal ulcer patients are subject to more stress than normal subjects or may be compensatory to increased vagal nervous activity presumed by some authors to be present in such patients.