Age-dependence of noradrenaline kinetics in normal subjects.

1. The influence of age on the rate of spillover of noradrenaline into plasma, clearance of noradrenaline from plasma, and plasma noradrenaline concentration at rest was studied in 34 healthy subjects aged 20--69 years. 2.

Effect of norepinephrine uptake blockers on norepinephrine kinetics.

We studied the effect of a single oral dose of the neuronal norepinephrine uptake blocker, desipramine 125 mg, on norepinephrine kinetics. Desipramine reduced the plasma norepinephrine clearance by approximately 20%, from 1.33 +/- 0.

Cardiac beta adrenoceptors and adenylate cyclase in normotensive and renal hypertensive rabbits during changes in autonomic activity.

The effects of hypertrophy and alterations in cardiac autonomic activity on left ventricular (LV) beta adrenoceptors and adenylate cyclase were measured in rabbits. Normotensive and renal hypertensive animals were exposed to three levels of chronic sympathetic activity: (i) "normal" activity; (ii) reduced activity after 2 weeks treatment with guanethidine; (iii) 2 weeks increased sympathetic activity following sino-aortic denervation. In hypertensive animals with "normal" activity LV beta receptor sarcolemma concentration was reduced by 36+ compared with the normotensive subgroup whilst total LV receptor numbers were unaltered.

Determination of noradrenaline uptake, spillover to plasma and plasma concentration in patients with essential hypertension.

1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state.

Assessment of neuronal uptake of noradrenaline in humans: defective uptake in some patients with essential hypertension.

1. Disappearance of tritiated noradrenaline from plasma, after infusion to steady-state, was studied to assess neuronal uptake of noradrenaline inessential hypertension. 2.

Simple and sensitive procedure for the assay of serotonin and catecholamines in brain by high-performance liquid chromatography using fluorescence detection.

A simple, rapid and specific method for the determination of serotonin and catecholamines in brain is described. After tissue homogenisation, catecholamines are isolated by adsorption onto alumina and elution with perchloric acid. Serotonin is isolated by extraction into n-heptanol and back-extraction into acid.

Interaction between oral propranolol and hydralazine.

Seven healthy subjects were given oral propranolol (1 mg/kg) alone or in combination with hydralazine 25, 50, or 100 mg on separate occasions. Hydralazine induced variable increases in the peak concentrations (p less than 0.05) and in the area under the propranolol concentration: time curves (p less than 0.

Norepinephrine kinetics in patients with idiopathic autonomic insufficiency.

The rates of norepinephrine release into plasma and removal from plasma were studied in patients with idiopathic peripheral autonomic insufficiency (sympathetic neuronal dysfunction), as it was thought that plasma norepinephrine concentration alone inadequately quantifies the degree of sympathetic nervous underactivity in this disorder. In four patients with autonomic insufficiency, clearance of norepinephrine from the circulation was slowed, 1.69 +/- 0.

Relationship between maximum chronotropic response to isoproterenol in man and generation of cyclic adenosine monophosphate by lymphocytes.

The maximum change in heart period caused by bolus doses of isoproterenol was measured in 10 normal subjects. This was linearly related to the amount of cyclic adenosine monophosphate generated from lymphocytes in the same subjects in vitro after incubation with isoproterenol. This high correlation between cardiac and lymphocyte beta-adrenoceptor stimulation suggests that maximum response does not depend on innervation.

Cardiac beta-adrenoceptors and adenylyl cyclase activity in rabbit heart during conditions of altered sympathetic activity.

Chronic (2 weeks) guanethidine treatment of rabbits depleted left ventricular noradrenaline and increased sarcolemmal beta-receptor density and protein yield. Total adenylyl cyclase activity was unchanged. Chronic sinoaortic denervation did not affect ventricular catecholamines and only marginally reduced beta-receptor numbers.

Study of noradrenaline uptake and spillover to plasma in normal subjects and patients with essential hypertension.

Noradrenaline uptake was studied in normal subjects, and in patients with essential hypertension. Uptake of noradrenaline by blood platelets was low-affinity in type. Platelets do not provide a satisfactory in vitro model of neuronal noradrenaline uptake.

Comparison of effectiveness of timolol administered once a day and twice a day in the control of blood pressure in essential hypertension.

The effects of a single dose and of two equally divided doses of timolol were compared in a double-blind trial in 15 patients with essential hypertension. The amount of timolol per day remained constant for each patient, but individual patients received different amounts (from 10 mg to 30 mg/day). Timolol combined with a diuretic produced similar lowering of blood pressure in patients who required 10 mg, 20 mg or 30 mg of timolol per day when given either as one dose or in two equal doses.

Absorption and excretion of rapid and slow release oxprenolol and their effects on heart rate and blood pressure during exercise.

1. Plasma concentrations and heart rate and blood pressure effects of 160 mg oxprenolol as standard rapid release (RR) and slow release (SR) tablets were compared in healthy volunteers. Peak plasma concentrations were lower with SR tablets than with RR tablets and the peak was delayed.

Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.

1 Pharmacokinetics of pindolol were studied in normal subjects given 5, 10 and 20 mg orally and 3 mg i.v. Plasma half time was 2.

Investigation of cardiac beta-adrenoceptors using 125I-labelled 1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol.

1-(4-iodophenoxy)-3-isopropylaminopropan-2-ol (IIP) is a potent beta-adrenergic antagonist which has been labelled to high specific activity with 125I and used to bind to rat myocardial membranes. The characteristics of binding were consistent with the known properties of beta-receptors. Thus, binding was highly stereospecific for the L-stereoisomer since L-propranolol was two orders of magnitude more potent than the D-isomer in competing for these sites.

Guanethidine-induced vasodilatation in the rabbit, mediated by endogenous histamine.

1 The effects of guanethidine (0.5-4 mg/kg i.v.

Inhibitors of hepatic mixed function oxidase. 3. Inhibition of hepatic microsomal aniline hydroxylase and aminopyrine demethylase by 2,6- and 2,4-dihydroxyphenyl alkyl ketones and related compounds.

A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor.

Leakage of dl-propranolol from cerebrospinal fluid to the bloodstream in the rabbit.

Intracerebroventricular (i.c.v.