1. Blood pressure measurements were made in hypertensive subjects after single intravenous and oral doses of labetalol and subsequently during chronic administration. 2. Oral therapy can be as effective as intravenous therapy in achieving acute blood pressure reduction. 3. Blood pressure control with chronic labetalol monotherapy was satisfactory in 11 of the 12 subjects. 4. High dose therapy with labetalol and 49 diuretic produced greater postural blood pressure falls.

1. The activities of the enzymes involved in catecholamine synthesis, tyrosine hydroxylase, aromatic amino acid decarboxylase and dopamine β-hydroxylase, were markedly enhanced in homogenates of phaeochromocytoma compared with human adrenal medulla homogenates measured under optimum substrate concentrations. 2. It was demonstrated in fresh tumour slices that the rate of formation of dopamine (3,4-dihydroxyphenethylamine) from tyrosine was much slower than the rate of formation of dopamine from dopa (3,4-dihydroxyphenylalanine) (suggesting that tyrosine hydroxylase was the rate-limiting enzyme in noradrenaline synthesis in phaeochromocytoma) and that the tyrosine hydroxylation step was still susceptible to end-product inhibition by catecholamines. 3. It is suggested that catecholamine overproduction in phaeochromocytoma is due to the increased activities of catecholamine synthetic enzymes rather than to an insensitivity of tyrosine hydroxylase to end-product inhibition. 4. The activities of the enzymes involved in catecholamine catabolism, monoamine oxidase and perhaps catecholamine O -methyltransferase, were reduced in phaeochromocytoma. This finding provides a biochemical basis for the previous published observations of nonexocytotic release of catecholamines in these tumours. Thus excess amounts of newly synthesized noradrenaline which cannot be stored in the filled catecholamine storage vesicles may not be degraded owing to the reduced monoamine oxidase activity and could diffuse from the phaeochromocytoma into the circulation.

1. The blood-bathed organ technique was employed to study the effects of angiotensin II and catecholamines on an isolated everted rat aorta bathed in the extracorporeal circulating blood of adult dogs and cats. 2. When the injections were made into the bathing blood close to the everted rat aorta, angiotensin II was half as potent as adrenaline or noradrenaline on a molar basis. 3. After intravenous injections, the vasoconstrictor potency of angiotensin was twenty times that of adrenaline or noradrenaline on the everted rat aorta. The increase in potency was due to the interaction of angiotensin II with catecholamines on the preparation. 4. Intravenous phenoxybenzamine abolished the potentiated vasoconstrictor effect of angiotensin II on the blood-bathed everted rat aorta, but it did not abolish the pressor effect of angiotensin II on the cardiovascular system of the animals. The results suggest that catecholamines released into the circulating blood by intravenous angiotensin II do not play an important role in the pressor effect of angiotensin II.

1. Studies with a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nervous system in essential hypertension. 2. Serotonin turnover in the mesenteric vessels is approximately twice that of noradrenaline and it is suggested that serotonin may interact with noradrenaline to maintain vascular resistance. 3. Methodology which allows the study of local sympathetic turnover in nuclei of the central nervous system and in peripheral blood vessels is described. This approach has been used to study non-innervated sympathetic turnover observed in phaeochromocytoma.

1. Mean plasma noradrenaline concentration was elevated in forty-four patients with established essential hypertension. Eighteen of these hypertensive patients had resting plasma noradrenaline concentrations in the normal range. 2. Patients with endogenous depression had higher mean plasma noradrenaline concentrations but significantly lower blood pressure than patients with essential hypertension. 3. Patients with phaeochromocytoma had plasma noradrenaline concentrations twenty-eight times greater than those found in essential hypertension, but blood pressures were less than 20% higher. 4. It is concluded that excess of sympathetic drive only partly explains the level of the blood pressure in essential hypertension.

1. Urinary sodium excretion and plasma renin activity have been measured in a group of persons with untreated mild hypertension and in a control normotensive group. 2. Preliminary analyses of the data indicate that the daily sodium excretion was significantly higher in the hypertensive group but the plasma renin activity did not correlate significantly with the urinary excretion of sodium. 3. These findings suggest that sodium intake was significantly greater in a population with mild hypertension than in a comparable normotensive group.

1. In thirty-one patients with essential hypertension there was a close relationship between resting diastolic blood pressure and basal plasma noradrenaline levels (r = 0.729, P<O.001). 2. After ganglionic blockade there was a highly significant correlation between change in resting blood pressure and change in plasma noradrenaline (r = 0.813, P<0*001). 3. Patients with the highest resting blood pressure had the largest falls in blood pressure and plasma noradrenaline. 4. These results suggest that the level of the blood pressure in essential hypertension is at least in part due to excess of sympathetic activity.

1. The levels of plasma renin activity or concentration and plasma angiotensin were similar in normotensive subjects and in untreated or treated essential hypertensives. 2. There was a close relationship between plasma renin activity and plasma renin concentration and between these and plasma angiotensin. This suggests that there were no abnormalities in renin substrate or renin kinetics in human essential hypertension. 3. Ganglion blockade did not change the plasma renin levels but α-adrenergic blockade caused a significant rise in plasma catecholamines and plasma renin without change in blood pressure. 4. Both acute and chronic β-adrenergic blockade were associated with a fall in blood pressure and small but significant falls in plasma renin levels.

1. Plasma dopamine β-hydroxylase (DβH) amounts were measured by radioimmunoassay in twenty-eight patients, twenty of whom had essential hypertension. There was a positive correlation between resting diastolic blood pressure and plasma DβH concentration. 2. Plasma DβH amounts also correlated significantly with those of plasma noradrenaline (NA) in individual patients. 3. These findings provide further support for the conclusions drawn from studies of plasma catecholamines that the sympathetic nervous system contributes toward the maintenance of the elevated blood pressure in essential hypertension.

1. Plasma catecholamine and dopamine β-hydroxylase (DβH) amounts were measured in a series of patients with proven phaeochromocytoma and compared with those of a group with essential hypertension. 2. Circulating catecholamine amounts were greatly elevated in phaeochromocytoma but plasma DβH was not significantly raised. 3. There was a significant correlation between plasma noradrenaline and DβH in individuals with essential hypertension but not with phaeochromocytoma. 4. The relative deficiency of DβH secretion in phaeochromocytoma indicates that the mechanism of release of catecholamines from these tumours does not involve the normal exocytosis of catecholamine storage vesicles. This supports the hypothesis that the primary defect responsible for the hypertension is excessive synthesis of catecholamines that bypass the normal storage and secretion mechanisms and diffuse into the circulation.