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Biomedical subjects

C A Hamilton

Publications and source records attributed to C A Hamilton.

At least 145 records · Page 8Linked to original sources

Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man.

Six normotensive volunteers were infused with L-adrenaline at 0.01, 0.03, 0.05, 0.075 and 0.10 microgram/kg-1 min-1, each increment lasted 10 min. Plasma adrenaline rose from 0.27 to 4.61 nmol/l, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0.083 +/- 0.006 microgram kg-1 min-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1.40 to 6.01 nmol/min with a mean (+/- SEM, 6) of 2.82 +/- 0.76 nmol/min. Mean clearance (+/- SEM, 6) was 9.41 +/- 1.37 l/min and ranged from 4.86 to 14.61 l/min. The decline of plasma adrenaline following the infusion was biexponential. Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.

Adult↗

The biochemical diagnosis, localization and follow up of phaeochromocytoma: the role of plasma and urinary catecholamine measurements.

The diagnosis of phaeochromocytoma is dependent on combined biochemical and radiological investigation, the biochemical studies being performed initially and followed later by both non-invasive and invasive radiological techniques. In 23 patients studied, a selection of biochemical studies allowed diagnosis and accurate localization of phaeochromocytoma in 16. In some patients, tumour localization was confirmed by radiographic methods. Biochemical estimations of catecholamines and/or metabolites in urine and/or plasma were also performed during and after operation, and these measurements allowed monitoring of the completeness of tumour excision, and of the possibility of recurrence, in both the short term and the long term follow up of patients.

Adrenal Gland Neoplasms↗

Interindividual variation in kinetics of infused epinephrine.

1-Norepinephrine was infused continuously for 10 hr into 5 normotensive, male laboratory subjects (mean age, 32.4 +/- 1.9 yr) at a mean rate of 0.06 microgram/kg/min. Mean plasma norepinephrine (NE) rose from the preinfusion level of 0.19 +/- 0.02 microgram/l to a steady state level of 1.22 +/- 0.29 microgram/l. The mean increase in blood pressure was 21.8 +/- 0.9 mm Hg systolic and 14.1 +/- 1.0 mm Hg diastolic. The mean depression in heart rate was 12.7 +/- 1.7 beats/min. The clearance of norepinephrine ranged from 27.9 to 100.0 ml/kg/min (mean. 58.0 +/- 13.8) and was little influenced by acute hemodynamic changes. The volume of distribution ranged widely (0.09 to 0.40 l/kg), the mean value being 13.51 1. The mean norepinephrine half-life was brief, ranging from 1.45 to 2.9 min (mean, 2.09 +/- 0.34 min). There was no evidence of a slowly accumulating high-capacity low-affinity pool of norepinephrine. These results support the use of plasma norepinephrine as an index of sympathetic activity within an individual but not its validity in interindividual comparisons.

Adult↗

Blood pressure and plasma noradrenaline during single high-dose beta adrenoceptor blockade.

The acute effects upon blood pressure and sympathetic outflow of two beta adrenoceptor blocking drugs, propranolol and atenolol, are described in five healthy normotensive subjects. Supine blood pressure, heart rate, plasma noradrenaline, and urinary catecholamine excretion were measured before and at intervals for 24 h after a single oral dose of either propranolol 200 mg, atenolol 100 mg, or placebo. Propranolol caused a fall in blood pressure and heart rate of 17.2/14.1 mm Hg and 20.4 beats/min respectively two hours after dose. Atenolol caused a fall in blood pressure of 11.4/18.6 mm Hg within 7 h of the dose, and a fall in heart rate of 13.8 beats/min after 2 h. The reduction in blood pressure after single high dose beta adrenoceptor blockade is established. The synchronous reduction in blood pressure and heart rate after propranolol was not associated with an increase in peripheral sympathietic activity as assessed by the biochemical indices. It is conceivable that the reduction in blood pressure during beta adrenoceptor blockade may be due in part to inappropriately low sympathetic activity but this cannot be the main mechanism of pressure reduction.

Adrenergic beta-Antagonists↗

The effects of desmethylimipramine on the pharmacological actions of alpha methyldopa in man.

The effect of pretreatment with the tricyclic antidepressant desmethylimipramine (DMI) 75 mg daily for 3 days on the action of oral methyldopa 750 mg was investigated in a double blind crossover design in volunteers. DMI pretreatment caused a small but not significant increase in supine systolic and diastolic blood pressure and heart rate. However, the effects of methyldopa on lying and standing blood pressure and heart rate were not markedly altered by pretreatment. In particular, the fall in standing blood pressure after methyldopa was present with and without DMI and the sedative action of methyldopa was similar. DMI alone reduced saliva production. No evidence was found that tricyclic antidepressant drugs significantly modify the hypotensive effect of methyldopa in man.

Adult↗

Choice of control groups in the appraisal of sympathetic nervous activity in essential hypertension.

1. Plasma noradrenaline concentrations were similar in normotensive and hypertensive outpatients, but were significantly lower in laboratory control subjects. 2. Standing plasma noradrenaline concentrations were similar in all three groups. 3. Urinary vanillyl mandelic acid, catecholamines and metanephrines were also similar in the normotensive and hypertensive groups. 4. Laboratory controls, possibly because of familiarity with the techniques of sphygmomanometry and blood sampling, may attain a 'basal' resting level of sympathetic nervous discharge more readily and rapidly than subjects who are unfamiliar with such procedures. 5. After orthostatic stimulation by standing for 2 min, the activity of the sympathetic nervous system, as determined by pulse rate and plasma noradrenaline concentrations, was similar in the three groups, despite the lower starting values in the laboratory staff. 6. The absence of differences in plasma noradrenaline or urinary catecholamine and metabolite concentrations does not support the hypothesis of excessive sympathetic nervous activity in essential hypertension.

Humans↗

Clonidine and sympathetic activity during sleep.

1. Blood pressure, heart rate, plasma noradrenaline and electroencephalographic variables were measured simultaneously during sleep in five healthy males before and after slow-release clonidine (300 micrograms orally) or placebo. 2. The blood pressure fall during sleep correlated significantly with the depth of sleep. 3. Clonidine significantly reduced systolic blood pressure during sleep and profoundly reduced total paradoxical sleep duration. 4. Plasma noradrenaline declined progressively during the sleep period and concentrations were significantly lower after clonidine compared with placebo.

Adult↗

Selective venous sampling in the diagnosis and localization of phaeochromocytoma.

Plasma noradrenaline levels were measured at several sites in the systemic venous system by selective catheterisation in ten hypertensive patients in whom phaeochromocytoma was suspected on clinical or biochemical grounds. Four patients had localized noradrenaline elevation and the diagnosis of phaeochromocytoma was confirmed at operation. The remaining six patients demonstrated no localized elevation of noradrenaline and there has been no evidence of a tumour on follow up. The technique allows the diagnosis and accurate localization of phaeochromocytoma and is useful in excluding the tumour in patients with essential hypertension.

Adrenal Gland Neoplasms↗

Plasma noradrenaline, age and blood pressure: a population study.

1. Mean supine plasma noradrenaline was lower in 12 male laboratory staff (0.24 +/- 0.02 microgram/l) than similarly normotensive out-patients (0.44 +/- 0.07 microgram/l). 2. In 164 non-medical hospital staff, plasma noradrenaline increased with age in white males only. 3. Plasma noradrenaline was significantly higher in women than men. 4. There was no relationship between supine blood pressure and plasma noradrenaline in normotensive or hypertensive subjects.

Adult↗

Sympathetic nervous function and renin activity in hypertensives on long term drug treatment with propranolol, methyldopa or bendrofluazide.

Plasma noradrenaline and plasma renin activity were measured as indices of sympathetic activity and renin angiotensin system in similar groups of hypertensive patients receiving either propranolol, bendrofluazide or methyldopa. Plasma renin activity was similar in the propranolol and methyldopa groups and significantly lower (p less than 0.01) in both these groups than the diuretic treated subjects. Plasma noradrenaline was significantly lower (p less than 0.01) on methyldopa than either propranolol or bendrofluazide. These different effects on the renin angiotensin system and the sympathetic nervous system of these drugs may be relevant in the choice of long term therapy in hypertension.

Adult↗

Clonidine withdrawal in hypertension. Changes in blood-pressure and plasma and urinary noradrenaline.

Treatment was interrupted abruptly in 6 hypertensive patients receiving clonidine 0-45-5-4 mg daily. Blood-pressure rose to pretreatment levels within 24-48 h of withdrawal and was accompanied by insomnia, headache, flushing, sweating, and apprehension. These symptoms began 18-20 h after the last dose of clonidine. Plasma-noradrenaline levels and urinary catecholamine excretion increased 24-72 h after withdrawal of clonidine. The subjective symptoms were most prominent in patients on higher doses (greater than 1 mg/day) and in those who had previously been receiving treatment with other antihypertensive drugs. One patient on a very low daily dose (0-15 mg) of clonidine had no symptoms and no significant changes in blood-pressure or catecholamine production after drug withdrawal.

Adult↗

Effects of clonidine on biochemical indices of sympathetic function and plasma renin activity in normotensive man.

1. A single oral dose of clonidine hydrochloride (300 microgram) lowered systolic blood pressure by 20+/-2 mmHg and diastolic blood pressure by 15+/-2 mmHg in seven healthy normotensive subjects. 2. Resting supine plasma noradrenaline concentration fell from 2-42+/-0-47 nmol/l before dosing to a minimum of 0-59+/-0-18 nmol/l at 6 h. The value subsequently rose and was not significantly different from that before the dose at 12 h. There was a significant reduction in urinary free catecholamine excretion in the first 12 h after dosing. 3. Resting supine plasma renin activity before dosing was 0-95+/-0-16 pmol of angiotensin I h-1 ml-1 of plasma and rose significantly after clonidine to 3-50+/-0-39 pmol of angiotensin I h-1 ml-1 of plasma at 6 h. By 12 h plasma renin activity had returned to control values. 4. When the same subjects were studied on a control, drug-free, day under the same conditions, there was no significant change in blood pressure or plasma noradrenaline. Although plasma renin activity rose during this control day, it was significantly lower than after clonidine. 5. In normotensive subjects single doses of clonidine lower blood pressure and are associated with a reduction of sympathetic nervous activity. Delayed elevation of plasma renin activity may be secondary to the fall in blood pressure. There is no evidence for an overshoot of sympathetic activity after a single dose of clonidine.

Adult↗