Search

To investigate the role of glucose and insulin in the development of hypotension following glucose ingestion in elderly subjects with orthostatic hypotension, the autonomic responses to glucose and xylose ingestion were studied in five elderly subjects with age related orthostatic hypotension (without autonomic failure), five elderly control subjects and three elderly subjects with evidence of autonomic failure. Heart rate, blood pressure, plasma noradrenaline and plasma arginine vasopressin responses to glucose ingestion and to xylose ingestion were investigated. All subjects were supine for 90 min following ingestion of each carbohydrate and were then tilted 45 degrees head-up for 10 min. Blood pressure was maintained in elderly control subjects following ingestion of both carbohydrates and during tilting. The elderly group with orthostatic hypotension, while supine had a fall in systolic blood pressure 60-90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60-90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestions; plasma noradrenaline levels after 2 min and plasma arginine vasopressin levels after 10 min tilting were significantly less following glucose ingestion compared to xylose ingestion. The autonomic failure group while supine had a fall in systolic blood pressure 60-90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60-90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestion. Plasma noradrenaline and arginine vasopressin levels were unchanged after ingestion of either carbohydrate, and during tilting.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to investigate whether orthostatic hypotension in elderly people is due to autonomic nervous system dysfunction or blood vessel abnormalities, we have measured platelet and lymphocyte adrenoceptor numbers and agonist binding in addition to venous plasma catecholamine concentrations. Eight elderly subjects with orthostatic hypotension and six control elderly subjects were studied. None of the subjects had other symptoms of autonomic failure. There was no significant difference between the heart rate or plasma catecholamine responses to standing of the two groups. The orthostatic hypotension subjects had a significant rise of their plasma vasopressin levels whereas the control group had no significant change. The number of alpha 2-adrenoceptor sites in platelets was lower in the orthostatic hypotensive group compared to the controls and the binding affinity was greater than in the controls. There were no significant differences in beta-adrenoceptor binding sites or affinities in isolated lymphocytes between the two groups. The similar changes in heart rate and catecholamines together with the vasopressin changes suggest that, in these elderly patients with an abnormal drop of blood pressure on standing, there is no dysfunction of autonomic pathways concerned with cardiovascular function. The lower numbers of alpha 2-adrenoceptor sites on isolated platelets in subjects with orthostatic hypotension could indicate reduced alpha 2-adrenoceptor numbers on their blood vessels which could contribute to their inability to maintain blood pressure while standing.

The clinical response of treatment with a chemical preparation of tyramine and tranylcypromine, a monoamine oxidase inhibitor, is described in six patients wit neurogenic orthostatic hypotension. Previous therapy with fluorocortisone, ephedrine, elastic garments, postural training and, in one patient, an anti-G suit was unsuccessful. Oral and intravenous tyramine produced no pressor response. However, after treatment with tranylcypromine five of the patients when supine showed a marked rise of blood pressure to intravenous tyramine which was sustained for over two hours when they stood up. Tyramine given orally with tranylcypromine produced a moderate rise of blood pressure in the supine position which was sustained for over 3-4 hours in the erect position enabling patients to walk about without symptoms of orthostatic hypotension. Measurement of circulating adrenaline and noradrenaline during therapy suggested that the pressor response was due to release of noradrenaline. Three patients have had marked improvement for four, fifteen and twenty-four months respectively. In a further patient, therapy has been successful in treating his orthostatic hypotension although his mobility has been restricted due to cerebellar ataxia. One patient developed a confusional state during treatment and the therapy was stopped. The only patient in whom the drugs produced no pressor response had orthostatic hypotension with evidence of adrenergic innervation of blood vessels, but failure of noradrenaline release. It is suggested that the pressor response to a monoamine oxidase inhibitor and tyramine should be examined in patients to a monoamine oxidase inhibitor and tyramine should be examined in patients with neurogenic orthostatic hypotension in whom conventional therapy is unsatisfactory and those who respond should receive a trial of this treatment.

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.

A 26 year old man is described with life-long orthostatic hypotension unrelated to autonomic nerve degeneration and apparently due to failure of peripheral noradrenaline realese. Tests of parasympathetic and sympathetic cholinergic nerve function were normal, but sympathetic adrenergic activity was defective. Thus blood pressure regulation was abnoraml. There was no pressor response to tyramine, an indirect sympathomimetic drug, but a marked pressor response to the directly acting sympathomimetic drugs phenylephrine and noradrenaline. On standing there was a progressive fall rather than a rise in circulating noradrenaline concentrations, although adrenaline levels rose normally. The pupils showed diminished responses to ephedrine and cocaine, and a normal response to phenylephrine. Fluorescence microscopy of blood bessels showed that they were innervated with adrenergic nerves. His orthostatic hypotenstion responded well to oral phenylephrine (50 mg five times daily) but not to other forms of therapy. It is suggested that this patient's symptoms were due to failure of noradrenaline release even though sympathetic adrenergic nerves were present. We therfore wish to draw attention to a further cause of orthostatic hypotension, failure of peripheral noradrenaline release without autonomic neuropathy.

It is now recognized that orthostatic hypotension occurs as a complication of many neurological diseases. An account is given of some of those in which it may develop. The pathological lesions frequently allow studies to be made of physiological mechanisms remaining in the isolated parts of the nervous system. For example transection of the cervical spinal cord causes complete separation of peripheral sympathetic pathways from the control of the brain. It was possible, therefore, to examine the control of renin release and also cerebral blood flow regulation during change of blood pressure in patients with some of these disorders. Evidence has been obtained that the renin-angiotensin system is active in paraplegia and in many other patients with orthostatic hypotension. In addition symptoms of cerebrovascular insufficiency are minimized by the retention of autoregulation of cerebral blood flow (CBF) in patients with failure of sympathetic function. Autoregulation maintains CBF within wide limits of blood pressure and symptoms of orthostatic hypotension only develop if the blood pressure falls below the lower limit, usually about 70 mm Hg.

The cardiovascular and plasma catecholamine responses to oral glucose (50 g) ingestion were investigated in five elderly subjects with orthostatic hypotension and five elderly control subjects. All the orthostatic hypotension subjects showed blood pressure falls after glucose ingestion, as compared to only one of the control subjects. Significantly greater falls in the orthostatic hypotension as compared to control patients were observed for systolic blood pressure (P less than 0.01) at 60 and 90 min following glucose and mean blood pressure (P less than 0.05) at 60 min following glucose. The orthostatic hypotension subjects did not have evidence of reduced heart-rate or plasma catecholamine responses to the glucose ingestion. It is concluded that, in elderly patients with orthostatic hypotension, disorder of blood pressure control may also cause hypotension associated with eating.

A patient with peripheral neuropathy and orthostatic hypotension was found to have pernicious anaemia. Symptoms improved after vitamin B12 replacement therapy. Insulin tolerance testing showed that the patient lacked catecholamine, heart rate, and sweating responses to hypoglycaemia. This indicates that pernicious anaemia may cause orthostatic hypotension owing to failure of noradrenaline release.

Two patients (aged 46 and 49 years) are presented who gave a history of several years' duration of unsteadiness, dizziness, and syncopal attacks on standing. Both had orthostatic hypotension which was associated with the development of a unifocal paroxysmal ventricular tachycardia. There was no evidence of organic heart disease. In one of the patients the symptoms usually developed when standing after working in a crouched position. He responded to treatment with beta-adrenergic blockade. The other patient developed her symptoms on standing, after exercise or other stress. The paroxysmal ventricular tachycardia, which occurred in the upright position only, was accompanied by a marked rise in plasma adrenaline. In this patient one contributory factor was a low blood volume and she responded to plasma volume expansion. We wish to draw attention to the common neurological symptoms with which paroxysmal ventricular tachycardia may present. We suggest that paroxysmal ventricular tachycardia may result from ventricular sensitivity to circulating adrenaline and not due to aberrant innervation of the heart as has been suggested previously.

Two patients who presented with symptoms due to orthostatic hypotension were found on examination to have the Holmes-Adie syndrome. Physiological investigation suggested that they both had an afferent block from baroreceptors in contrast to the efferent autonomic block found in most other cases of idiopathic orthostatic hypotension, including the cases of multisystem disease, now often called the Shy-Drager syndrome.