Acute and long-term effects of acebutolol on systemic and renal hemodynamics, body fluid volumes, catecholamines, active renin, aldosterone, and lymphocyte beta-adrenoceptor density.

Acebutolol is a relatively new beta-adrenoceptor blocking antagonist, possessing both beta 1-adrenoceptor selectivity and partial agonist activity (PAA). Its acute (24 h, 400 mg, twice daily) and long-term effects (3 weeks) on systemic and renal hemodynamics, body fluid volumes, hormones, and beta-adrenoceptor density on lymphocytes were studied in a single-blind placebo-controlled trial, in 10 hypertensive patients. The initial response to acebutolol (1-2 h) was a fall in heart rate (HR) (-9.

Effect of unnatural noradrenaline precursor on sympathetic control and orthostatic hypotension in dopamine-beta-hydroxylase deficiency.

A patient with severe orthostatic hypotension due to dopamine-beta-hydroxylase deficiency was treated with the unnatural aminoacid D,L-threo-3,4-dihydroxyphenylserine (DOPS) in the hope that it would serve as a substrate of aromatic-L-aminoacid decarboxylase to produce (-)-noradrenaline. With a dose of 500 mg twice daily by mouth, blood pressure rose gradually from 100/55 to 145/85 mm Hg, and orthostatic hypotension disappeared. After 4 months' treatment the patient is free of symptoms and able to live a normal life.

The clinical pharmacology of bopindolol, a new long-acting beta-adrenoceptor antagonist, in hypertension.

Bopindolol is a new long-acting, nonselective beta-adrenoceptor antagonist with partial agonist activity. Its acute (24 hours, 2 mg, administered orally) and long-term (3 weeks, 2 to 4 mg) hemodynamic and hormonal effects were studied in a single-blind placebo-controlled trial in 10 hypertensive subjects. The initial response (mean +/- SE) to bopindolol was a fall in cardiac output (-12% +/- 2%) and heart rate (-11% +/- 2%).

Sodium restriction and potassium supplementation in young people with mildly elevated blood pressure.

Forty young subjects, aged 18 to 28 years, with mildly elevated blood pressure participated in a double-blind randomized three-period crossover study of the effect of sodium restriction with and without potassium supplementation on blood pressure. Dietary sodium intake was restricted for 18 weeks in which the patients received in random sequence 'slow-sodium' (90 mmol/day), 'slow-potassium' (72 mmol/day), and placebo tablets, each for 6 weeks. Mean urinary sodium excretion was 129 mmol/24 h in the slow-sodium period, 57 mmol/24 h during placebo, and 69 mmol/24 h during slow-potassium.

Is beta 1-antagonism essential for the antihypertensive action of beta-blockers?

Both nonselective beta-blockers and beta 1-selective blockers are effective antihypertensive agents. beta 1-Blockade generally is considered to be responsible for their antihypertensive action, whereas beta 2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which beta-blockers lower blood pressure remains unknown.

Congenital dopamine-beta-hydroxylase deficiency. A novel orthostatic syndrome.

A woman was referred with severe orthostatic hypotension at the age of 21. Ptosis, skeletal muscle hypotonia, and recurrent hypoglycaemia had been noticed in early childhood. There was noradrenergic denervation and adrenomedullary failure but baroreflex afferents, cholinergic innervation, and adrenocortical function were intact.

Determination of aromatic-L-amino acid decarboxylase in human plasma.

Aromatic-L-aminoacid (dopa) decarboxylase (ALAAD) was determined in human plasma by its ability to form dopamine from the substrate 3,4-dihydroxyphenylalanine in the presence of pyridoxal-5-phosphate as cofactor. Dopamine formed was quantitated by high performance liquid chromatography with electrochemical detection. A preincubation step of plasma with the cofactor and dithioerythritol was necessary to obtain optimal reaction conditions.

Stress levels of adrenaline amplify the blood pressure response to sympathetic stimulation.

The possibility that sympathetic pressor responses are modulated by adrenaline-mediated facilitation of neuronal noradrenaline release was explored in 17 subjects with borderline hypertension. Infusion of adrenaline, which raised plasma adrenaline by a factor of 8 to 9, augmented the rise in systolic and diastolic arterial pressure induced by standardized cold pressor and isometric exercise tests. The heart rate response to these tests was not affected.

Compound ICI 118,551, a beta 2-adrenoceptor antagonist, lowers blood pressure.

Adrenaline may increase noradrenaline release and enhance sympathetic pressor effects through activation of pre-synaptic beta 2-adrenoceptors. Conversely, blockade of beta 2-receptors could lead to a fall in blood pressure. To test this hypothesis we performed a double-blind placebo controlled crossover study in nine patients with mild hypertension, comparing the effects of the beta 2-selective blocker ICI 118,551, 50 mg t.

Cyclic blood pressure changes in a patient with a phaeochromocytoma: role of a central oscillator?

During continuous intra-arterial pressure monitoring in an 18-year-old man with severe hypertension and a phaeochromocytoma we registered marked oscillations in blood pressure with a cycle length of 3 min (range 2-4 min) and amplitude of 40 mmHg (range 12-80 mmHg). Changes in heart rate were opposite to changes in pressure. The pressure waves almost invariably appeared at rest and were most prominent during sleep.

Prevention of epinephrine-induced hypokalemia by nonselective beta blockers.

Experimental evidence is presented that activation of beta 2 adrenoreceptors causes a dose-dependent decrease in plasma potassium, probably by shifting potassium into the cell. By this mechanism epinephrine may cause hypokalemia and predispose to cardiac arrhythmias. Prevention of these effects by nonselective beta blockers may contribute to the cardioprotective action of these drugs.

Ketanserin: a possible tool for studying the role of serotonin in hypertension.

Ketanserin is a serotonin antagonist with high affinity for S2-serotonergic receptors, which mediate the vasoconstrictor effects of serotonin. It does not block the vasodilator effects of this monoamine, and it is devoid of agonist activity and serious central side effects. Ketanserin, however, also binds to alpha 1-adrenoceptors.

Effects of selective and nonselective beta-agonists on plasma potassium and norepinephrine.

The effects of graded infusions of the beta-agonists isoproterenol (nonselective), l-prenalterol (beta 1-selective), and salbutamol (beta 2-selective) on plasma potassium and norepinephrine were compared in subjects with borderline hypertension. Potassium levels fell with all three agonists, and norepinephrine levels rose with isoproterenol and salbutamol. These effects on potassium and norepinephrine were closely correlated and occurred at the same dose ranges as the cardiovascular responses.

Evaluation of a test kit for the rapid and simple colorimetric measurement of angiotensin I-converting enzyme in serum.

We have evaluated a recently introduced colour test kit for the determination of serum angiotensin I-converting enzyme catalytic activity. p-Hydroxyhippuric acid, liberated from p-hydroxyhippuryl-L-histidyl-L-leucine by angiotensin I-converting enzyme, is converted into a quinoneimine dye with an absorption maximum at 505 nm. The procedure shows excellent linearity over the whole range of catalytic activities found in serum.

Beta-receptor stimulation by adrenaline elevates plasma noradrenaline and enhances the pressor responses to cold exposure and isometric exercise.

Isoprenaline 3.5-35 ng/kg/min, salbutamol 17.5-175 ng/kg/min and prenalterol 1-32 micrograms/kg were given intravenously (i.

Cardioprotection by blockade of beta 2-adrenoceptors.

The effects of different beta-adrenoceptor agonists and antagonists on plasma noradrenaline and potassium concentrations were studied in patients with borderline hypertension. Heart rate, arterial pressure and the heart rate corrected duration of total electromechanical systole (QS2I) were also measured. Infusion of the beta-adrenoceptor agonists isoprenaline (non-selective) and salbutamol (beta 2-selective), but not prenalterol (beta 1-selective) caused dose-dependent increments in plasma noradrenaline.

Asynchronous changes in prorenin and renin secretion after captopril in patients with renal artery stenosis.

An assay of plasma prorenin was developed in which the conversion to renin occurred under apparently optimal conditions. Some characteristics of the assay were 1) prorenin was activated by Sepharose-bound trypsin at 4 degrees C; 2) the concentration of activator was not critical provided that incubation was prolonged until renin activity had reached a plateau; and 3) this plateau was stable and had the same height as after maximal activation with acid, pepsin, plasmin or urokinase. Maximal activity with Sepharose-bound trypsin at 4 degrees C was higher than with cryoactivation, and optimal conditions were more readily reproduced than with trypsin at 37 degrees C or with acid-activation.

Effects of captopril in acute and chronic heart failure. Correlations with plasma levels of noradrenaline, renin, and aldosterone.

The angiotensin-converting enzyme inhibitor, captopril, was given to 19 patients with severe heart failure. Seven patients had acute myocardial infarction and the remainder had chronic myocardial damage caused by ischaemia or valvular disease. Cardiac filling pressures were raised in all, the pulmonary capillary "wedge" pressure being 17 mmHg or more.

Elevated plasma noradrenaline in response to beta-adrenoceptor stimulation in man.

Dose-dependent increments of plasma noradrenaline were observed during graded infusions of (±)isoprenaline (3.5-35 ng kg min i.v.

Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist.

The new selective 5-HT2 receptor blocking agent ketanserin was given in a dose of 10 mg intravenously to 12 patients with essential hypertension. It caused a distinct fall in supine systemic arterial, right atrial, pulmonary artery, and pulmonary capillary "wedge" pressures. Cardiac output, renal blood flow, and glomerular filtration rate showed no persistent changes.

Activation of plasma prorenin by plasminogen activators in vitro and increase in plasma renin after stimulation of fibrinolytic activity in vivo.

Plasminogen can be activated by intrinsic activators that circulate in plasma in a precursor form, by extrinsic activator originating from tissues or the vessel wall and by the exogenous activators, urokinase and streptokinase. Tissue activator and vascular activator are probably identical. Dialysis of plasma against pH 4.

Effects of beta-adrenoceptor agonists and antagonists in patients with peripheral autonomic neuropathy.

Four patients with orthostatic hypotension due to peripheral autonomic neuropathy were studied. The diagnosis was based on severe hypotension during 60-degrees head-up tilting and absence of the systolic pressure overshoot in phase IV of the Valsalva response. Plasma noradrenaline levels were less than 25 pg/ml in two patients and between 50 and 90 pg/ml in the remainder.