Biomedical subjects

F Boomsma

Publications and source records attributed to F Boomsma.

At least 145 records · Page 8Linked to original sources

PubMed1989

Characterization of stress reactions to the Stroop Color Word Test.

Sympatho-adrenal activation induced by stress contributes to the development of pathological states such as hypertension and anxiety disorders. The Stroop Color Word Test (CWT) is evaluated as a test for the study of stress-induced sympathetic effects, on the basis of psychological, physiological and biochemical responses. The CWT induced increases in plasma and urinary adrenaline, heart rate, respiration rate, electrodermal activity, electromyography, feelings of anxiety, and decreased finger pulse amplitude.

Adult↗

PubMed1989

Combined measurements of plasma aromatic L-amino acid decarboxylase and DOPA as tumour markers in diagnosis and follow-up of neuroblastoma.

As neuroblastoma, the most common solid tumour in childhood, may contain all the constituents of the catecholamine biosynthesis cascade, some of these constituents may be produced in excess in a varying mixture reflecting the wide variability in expression of differentiated features of the tumour. We have measured plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA) and 3,4-dihydroxyphenylalanine (DOPA), and plasma activities of dopamine beta-hydroxylase (DBH) and aromatic L-amino acid decarboxylase (ALAAD) in 18 patients with neuroblastoma, in 13 at various times during the course of their disease. Activities of serum lactic dehydrogenase (LDH), serum levels of ferritin (FER) and neuron-specific enolase (NSE), and urinary vanilmandelic acid (VMA) were also determined. NE, E and DBH were found not to reflect tumour activity. In untreated active neuroblastoma DOPA or ALAAD (10 out of 10) or both (six out of 10) were clearly elevated. In all 13 patients where samples were obtained during chemotherapy, ALAAD activities fell within the normal range, while DOPA decreased more slowly. During relapse, DOPA and, especially, ALAAD, rapidly increased; in all six patients who had a relapse both DOPA and ALAAD were elevated. In complete remission (eight patients), ALAAD was normal in all patients, but DOPA remained elevated in the one patient who later experienced a relapse. Our preliminary conclusion is that combined measurements of plasma ALAAD and DOPA may be useful markers for neuroblastoma activity at diagnosis, but even more so in indicating residual disease (DOPA) and in the early detection of relapse (ALAAD).

Aromatic-L-Amino-Acid Decarboxylases↗

PubMed1989

Hemodynamic and beta-adrenergic receptor adaptations during long-term beta-adrenoceptor blockade. Studies with acebutolol, atenolol, pindolol, and propranolol in hypertensive patients.

In an attempt to further clarify the mechanism of the maintenance of the antihypertensive effect of beta-adrenoceptor antagonists, the effects of four antagonists with different ancillary properties (acebutolol, atenolol, pindolol, and propranolol) on systemic and renal hemodynamics, body fluid volumes, hormones, and lymphocyte beta-adrenoceptor density were studied in four groups of 10 hypertensive patients. The patients were observed for 3 weeks during active treatment and for 2 weeks after withdrawal of treatment. At the end of the 3-week treatment period, the four drugs had an equal antihypertensive effect (fall in mean arterial pressure, 10-13%). Although renin activity was suppressed (60-70%) by all four drugs, changes in renin or pretreatment values of renin levels were not correlated with the fall in blood pressure. The drugs had no effect on plasma catecholamine concentrations or body fluid volumes. Despite similar antihypertensive effects among the four drugs, the changes in flow and resistance underlying the fall in blood pressure differed considerably. With pindolol, the fall in blood pressure was associated with a fall in vascular resistance (26 +/- 6%), whereas with propranolol, it was predominantly associated with a fall in cardiac output (11 +/- 7%). No significant changes in vascular resistance or cardiac output occurred with atenolol or acebutolol. The changes in renal blood flow and renal vascular resistance occurred in parallel with the changes in cardiac output and systemic vascular resistance. Plasma epinephrine concentration and pretreatment cardiac chronotropic responsiveness to isoproterenol appeared to be inversely correlated with lymphocyte beta-adrenoceptor density (Bmax) (r = -0.41 and -0.43, respectively). With pindolol, Bmax decreased maximally by 39 +/- 6%, and with propranolol, it increased by 51 +/- 17%. With both drugs, significant changes in Bmax were already present 24 hours after treatment. Furthermore, 1 week after withdrawal of treatment with pindolol, Bmax was still down-regulated, and cardiac chronotropic responsiveness was still decreased, whereas 1 week after withdrawal of propranolol, Bmax was still up-regulated, and cardiac chronotropic responsiveness was still increased. No changes in Bmax occurred with the beta 1-selective antagonists acebutolol and atenolol. Thus, despite an equal antihypertensive effect, the four beta-adrenoceptor antagonists appear to have dissimilar effects on cardiac output, renal blood flow, and lymphocyte beta-adrenoceptors. Changes in cardiac output, the circulating blood volume, or angiotensin-mediated vasoconstriction are factors unlikely to be crucial for the antihypertensive effect of beta-adrenoceptor antagonists. Therefore, interference with vasoconstrictor nerve activity through blockade of either central or peripheral prejunctional beta-adrenoceptors could be an alternative explanation of their blood pressure-lowering potential.

Adaptation, Physiological↗

PubMed1989

Venous versus arterial forearm catecholamines as an index of overall sympatho-adrenomedullary activity.

The metabolism of norepinephrine (NE) and epinephrine (EPI) in peripheral tissues limits the use of venous plasma levels of these parameters as an index of overall sympathetic or adrenomedullary activity. Therefore venous (deep antecubital vein) and arterial (brachial artery) concentrations of NE and EPI were compared in 16 hypertensive subjects. NE and EPI were determined after 30 min supine rest, and immediately before and after isometric exercise, cold provocation, head-up tilting (OST) and Stroop's colour word test (CWT). At rest venous NE exceeds arterial NE. Assuming similar fractional extractions (FE) of NE and EPI, 46 +/- 14% (mean +/- SD) of venous NE appeared to be produced locally. Despite this considerable local production venous and arterial levels of NE were closely correlated (r = 0.92). At rest venous EPI was 42 +/- 13% lower than arterial EPI, but since the interindividual variation of the FE of EPI was relatively small and independent of arterial levels, venous and arterial levels were also closely correlated (r = 0.82). All four tests caused an increase in arterial and venous NE, whereas EPI did not change. Responses of arterial and venous NE were only correlated after OST and CWT. It is concluded that at rest, but not invariably so during different forms of sympatho-adrenal activation, arterial plasma concentrations of NE and EPI can be substituted for by their respective venous equivalents.

Adrenal Medulla↗

PubMed1988

Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.

In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.

Adult↗

PubMed1988

Determination of D,L-threo-3,4-dihydroxyphenylserine and of the D- and L-enantiomers in human plasma and urine.

DL-threo-3,4-Dihydroxyphenylserine (DOPS) is increasingly being investigated for treatment of disorders involving defects of the sympathetic nervous system, such as Parkinson's disease, Shy-Drager syndrome and congenital dopamine-beta-hydroxylase deficiency. Whilst L-DOPS is converted by aromatic L-amino acid decarboxylase into natural norepinephrine in vitro, D-DOPS inhibits this process. There are no data on the interaction between D- and L-DOPS in vivo because a reliable method for the measurement of the D- and L-enantiomers in plasma and urine is lacking. We describe here such a method based on reversed-phase chromatography after derivatization with o-phthaldialdehyde and N-acetyl-L-cysteine. Good separation was achieved with this procedure (resolution factor 2.33). Two simple and sensitive methods are also presented for total D,L-DOPS estimation, based on reversed-phase chromatography with electrochemical detection after either deproteinization (DP) or liquid-liquid extraction (LE) as sample preparation steps. The two methods gave identical results (regression line DOPS (DP) = 1.026 DOPS (LE) + 33.28; r = 0.997; n = 52). Excellent agreement was found between the sum of the D- and L-DOPS concentrations and the measured total D,L-DOPS concentration (regression line DOPS (D + L) = 0.955 DOPS (total, LE) + 116.65; r = 0.992; n = 100).

Acetylcysteine↗

PubMed1988

Determination of 3,4-dihydroxyphenylalanine (DOPA) in plasma and cerebrospinal fluid by high performance liquid chromatography with electrochemical detection.

We report a reliable method for determining DOPA levels in plasma and cerebrospinal fluid. The method is based on complete conversion of DOPA to dopamine and quantification by HPLC-ECD of the dopamine formed. Lower limit of detection was 0.5 nmol/l. No differences in plasma DOPA levels were found between normal children (0-15 yr, n = 60), normal adults (n = 39) and patients with essential hypertension (n = 40) or Parkinson's disease (no DOPA therapy, n = 30). In normal individuals and in patients with essential hypertension venous plasma levels were higher than arterial levels (10.2 vs 9.3 nmol/l, p less than 0.001, V/A ratio 1.11 (SD 0.08), n = 15). Sympathetic stimuli (standing, tilting, bicycle exercise, tyramine) did not influence DOPA levels. In untreated depressed patients (n = 10) and in non-parkinsonian neurological patients (n = 12) cerebrospinal fluid levels of DOPA were 4.5 (SD 2.4) and 5.2 (SD 1.3) nmol/l respectively. A direct method for the measurement of DOPA by HPLC-ECD after deproteinization of plasma is also described and compared with the conversion method. Good agreement was found when plasma DOPA levels exceeded 0.25 mumol/l (y(conversion method) = 0.943x (direct method) + 0.118; n = 60; r = 0.985). The direct method, because of greater simplicity and the possibility of simultaneous measurement of the DOPA metabolite 3-O-methyldopa, is the method of choice with plasma samples from DOPA-treated patients. In non-DOPA treated individuals the conversion method is superior and has proved to be an accurate and sensitive method for the determination of DOPA levels in plasma and cerebrospinal fluid.

Adolescent↗

PubMed1988

Patients with congenital dopamine beta-hydroxylase deficiency. A lesson in catecholamine physiology.

We recently described a case of congenital dopamine beta-hydroxylase (DBH) deficiency. The syndrome is characterized by noradrenergic denervation, adrenomedullary failure, but intact baroreflex afferents, cholinergic innervation, and adrenocortical function. Norepinephrine, epinephrine, and their degradation products were undetectable in plasma, urine, and cerebrospinal fluid, whereas dopamine and its degradation products were elevated. Plasma DBH was not detectable. Studies in this novel syndrome showed evidence for the peripheral production of dopamine from sympathetic nerve terminals noradrenergic in nature. Tyrosine hydroxylase is probably induced in this syndrome, since plasma levels of L-DOPA were also elevated. Absence of hemodynamic effects of sympathicolytic agents in the face of an increase in blood pressure after dopamine antagonists suggest that intrasynaptic concentrations of dopamine are in the range of its plasma concentrations. Hypoprolactinemia, reduced REM sleep, increased slow wave sleep and sodium loss, despite low blood pressure, are further evidence for the biological role of dopamine in man.

Adult↗

PubMed1988

d,l-threo-3,4-dihydroxyphenylserine restores sympathetic control and cures orthostatic hypotension in dopamine beta-hydroxylase deficiency.

Two patients with congenital dopamine beta-hydroxylase (DBH) deficiency were treated with d,l-threo-3,4-dihydroxyphenylserine (DOPS), 500 mg twice daily. In this orthostatic syndrome the functional integrity of the sympathetic noradrenergic neuron is probably intact, but dopamine instead of noradrenaline is released as the neurotransmitter. In vitro l-DOPS may serve as a substrate for aromatic-l-amino-acid decarboxylase (ALAAD) to form physiological (-)-noradrenaline. During infusion of d,l-threo-DOPS, 400 mg in 4 h, noradrenaline appeared in plasma and blood pressure rose, whereas plasma dopamine and the elevated venous:arterial ratio of plasma dopamine decreased. During chronic treatment supine blood pressure rose from 100-115/55-65 to 140-145/80-85 mmHg and orthostatic hypotension disappeared. After 12 and 6 months of treatment the patients are free of symptoms and they live a normal life. During chronic treatment, d,l-threo-DOPS, like plasma noradrenaline and dopamine, rose after standing, indicating release of the precursor after neuronal stimulation. After administration of tyramine plasma noradrenaline, dopamine and d,l-threo-DOPS and their respective venous:arterial ratios rose; this is further evidence of neuronal release. Thus, in DBH deficiency, dopamine instead of noradrenaline is released as a neurotransmitter, but the integrity of the sympathetic neuron is otherwise intact. Acting as an alternative substrate for ALAAD in the production of noradrenaline, DOPS is taken up by the neuron, restoring sympathetic control and thereby curing the orthostatic hypotension in DBH deficiency.

Blood Pressure↗

PubMed1988

Adrenaline-induced amplification of sympathetic activity during rest and stress: inhibition by non-selective and beta 1-selective beta-adrenoceptor blockade.

In a placebo-controlled randomized cross-over trial the effects of non-selective (bopindolol, 1 mg once daily for 1 week) and of beta 1-selective beta-adrenoceptor blockade (atenolol, 50 mg once daily for 1 week) on adrenaline-induced enhancement of basal and stimulated sympathetic activity were studied in 10 hypertensive subjects. During infusion of adrenaline (20 ng/kg per min) venous plasma adrenaline levels increased into the high physiological range. Resting concentrations of arterial plasma noradrenaline and of the basal production of noradrenaline in the forearm increased significantly (P less than 0.01) during infusion of adrenaline. The increases in these two indices of sympathetic activity were abolished by bopindolol and by atenolol. Arterial noradrenaline, but not noradrenaline production, also increased in response to isometric exercise, cold provocation and mental stress during infusion of adrenaline (P less than 0.05). These amplifications were also abolished by both beta-adrenoceptor antagonists. Our findings provide further evidence in man for a stimulatory effect of adrenaline in the physiological range on sympathetic activity. This effect, which is supposed to be mediated by prejunctional beta-adrenoceptors, can be blocked not only by non-selective, but also by beta 1-selective beta-adrenoceptor antagonists.

Adrenergic beta-Antagonists↗

PubMed1988

Twenty-four hour pressor effect of infused adrenaline in normotensive subjects: a randomized controlled double-blind cross-over study.

Stimulation of prejunctional beta 2-adrenoceptors on sympathetic nerve terminals increases vasoconstrictor nerve activity by facilitating release of noradrenaline. Therefore, man's endogenous beta 2-adrenoceptor agonist adrenaline has been implicated in the pathogenesis of hypertension. To test this hypothesis, adrenaline (15 mg/kg per min), noradrenaline (30 ng/kg per min) and saline (0.9% NaCl, 5.4 ml/h) were infused in 10 supine, resting healthy volunteers for 6 h (1000-1600 h) in random order 2 weeks apart in a double-blind crossover fashion. During infusion of noradrenaline and adrenaline, venous plasma concentrations rose to 705 +/- 58 (mean +/- s.e.m) and 230 +/- 28 pg/ml, respectively. Mean arterial pressure rose by 4% (P less than 0.001) during noradrenaline and fell by 5% (P less than 0.001) during the adrenaline infusion compared with the saline infusion. In the postinfusion period (1600-0900 h) mean arterial pressure was 7% higher (P less than 0.01) after adrenaline compared with the saline infusion, whereas after the noradrenaline infusion, values of mean arterial pressure were not different from those during the saline infusion. The pressor effect of adrenaline could not be explained by a central mechanism or by activation of the renin-angiotensin system. Thus, 'stress levels' of adrenaline mediate a delayed and protracted pressor effect. This is most likely due to stimulation of prejunctional beta 2-adrenoceptors, since 'stress levels' of noradrenaline are devoid of such activity. Our data support the 'adrenaline-hypertension' hypothesis in man.

Adult↗

PubMed1988

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) (-9.6 +/- 2.7%), cardiac output (-16.0 +/- 3%), and stroke volume (SV) (-10.7 +/- 0.2%), and an increase in systemic vascular resistance (SVR) (18.0 +/- 3.9%). Mean arterial pressure (MAP) began to fall 2-3 h after dosing in parallel with a decrease in SVR. At the end of the acute study, MAP and SVR were decreased by 18.1 +/- 2.7% and 15.6 +/- 5.6%, respectively. By that time, HR and SV had returned to control values despite blockade of beta-adrenoceptors. After 3 weeks of treatment (mean dose of acebutolol 480 mg twice daily), the fall in MAP was 10.1 +/- 2.7% and HR was decreased by 13.0 +/- 2.3%. Renal blood flow and glomerular filtration rate did not change. Acute and long-term treatment had no effect on the density of lymphocyte-membrane beta-adrenoceptors. This could be explained by acebutolol's beta 1 selectivity or, alternatively, this could be due to the drug's PAA.

Acebutolol↗

PubMed1988

Hemodynamic and hormonal adaptations to beta-adrenoceptor blockade. A 24-hour study of acebutolol, atenolol, pindolol, and propranolol in hypertensive patients.

Comparison of the hemodynamic and hormonal effects of beta-adrenoceptor antagonists with different ancillary properties may help to clarify the antihypertensive mechanism of these drugs. Under strict basal conditions, the effects of acebutolol (400 mg b.i.d.), atenolol (100 mg b.i.d.), pindolol (10 mg b.i.d.), and propranolol (80 mg t.i.d.), were studied for the first 24 hours in 40 hypertensive patients. With pindolol, mean arterial pressure was reduced (p less than 0.05) 1 hour after administration, whereas the cardiac index and the systemic vascular resistance index did not change. With the other three drugs, the fall in mean arterial pressure was delayed 2-3 hours. With these drugs, the fall in mean arterial pressure was preceded by a rise in the resistance index, which compensated for the initial fall in cardiac index. With each drug, the decrements in mean arterial pressure were associated with parallel decrements in the resistance index, and percent changes in mean arterial pressure and the resistance index were always significantly (p less than 0.001) correlated. At the end of the 24-hour period, the four drugs shared an equal antihypertensive effect, which varied 14-17%. This was associated with a return of the cardiac index toward control values by acebutolol, atenolol, and propranolol treatment and a moderately increased cardiac index above pretreatment values (13%, p less than 0.01) with pindolol. The secondary rise in the cardiac index was inversely correlated (p less than 0.001) with the fall in mean arterial pressure with all four drugs. Plasma renin was maximally suppressed 2 hours after treatment, thus before any change in mean arterial pressure had occurred with acebutolol, atenolol, and propranolol. Pretreatment values of active renin and the reduction of mean arterial pressure 24 hours after administration were not correlated in any of the four groups. Despite the "vasodilator" action of the four drugs, plasma norepinephrine did not rise. Our data show that the main hemodynamic change that occurs at the time blood pressure falls after beta-adrenoceptor antagonism is vasodilation. Neither autoregulation of blood flow nor renin suppression can explain this vasodilator action. The absence of an increase in norepinephrine, despite vasodilation, suggests that beta-adrenoceptor antagonism interferes with sympathetic vasoconstrictor nerve activity. This effect may explain the vasodilator and antihypertensive potential of beta-adrenoceptor antagonists.

Acebutolol↗

PubMed1987

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. DOPS switched on the production of noradrenaline and reduced the excessive production of dopamine. During treatment plasma noradrenaline rose normally after standing and after infusion of tyramine, a biogenic amine that liberates stored neurotransmitter from sympathetic nerve terminals. These data demonstrate that in congenital dopamine-beta-hydroxylase deficiency dopamine instead of noradrenaline is released as the sympathetic neurotransmitter but that the integrity of the sympathetic neuron is otherwise intact.

Aromatic-L-Amino-Acid Decarboxylases↗

PubMed1987

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. Noradrenaline and adrenaline were undetectable in plasma, urine, and cerebrospinal fluid (CSF), but dopamine was 7-fold to 12-fold normal in plasma, 4-fold normal in urine, and 20-fold normal in CSF. Measurements of catecholamine metabolites showed further evidence for impairment of noradrenaline and adrenaline biosynthesis due to deficient dopamine-beta-hydroxylation. Dopamine-beta-hydroxylase was undetectable in plasma and CSF. Physiological and pharmacological stimuli of sympathetic neurotransmitter release caused increases in plasma dopamine rather than plasma noradrenaline.

Adult↗

PubMed1987

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%). Mean arterial pressure began to fall 3 to 4 hours after administration in parallel with a decrease in systemic vascular resistance, which had increased initially. Twenty-four hours after administration, mean arterial pressure and systemic vascular resistance were reduced by 12% +/- 2% and 12% +/- 5%, respectively. By that time heart rate and cardiac output did not differ from baseline values despite beta-blockade. After 3 weeks of treatment mean arterial pressure had fallen by 9% +/- 2% and renal blood flow and glomerular filtration rate were not changed. One week after withdrawal from treatment mean arterial pressure and heart rate were no longer reduced, but beta-blockade could still be demonstrated, establishing the long duration of action of the drug.

Adrenergic beta-Antagonists↗

PubMed1987

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. Mean supine systolic blood pressure in the sixth week of the slow-potassium period was 3.3 mmHg lower than that at the end of the slow-sodium period (P less than 0.05). There was no significant difference in systolic or diastolic blood pressure between the placebo and the slow-sodium periods. The fall in systolic blood pressure in the low sodium/high potassium period was accompanied by a fall in cardiac index of 0.4 l/min per m2 body surface area (BSA) (P = 0.03). Our observations suggest a small hypotensive effect of moderate sodium restriction combined with high potassium intake in young hypertensive subjects. Sodium restriction alone has little effect on blood pressure in this group. The combination of a low sodium/high potassium diet may lower blood pressure by affecting cardiac output. Reducing the dietary sodium:potassium ratio may therefore be useful in the management of early primary hypertension.

Adolescent↗

PubMed1987

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. To examine the possibility that beta 2-blockade may contribute to the antihypertensive action of beta-blocker therapy, we studied the cardiovascular effects of compound ICI 118551, a beta 2-selective blocker. First, we showed that 50 mg t.i.d. orally is a beta 2-selective dose. In contrast to propranolol, 80 mg t.i.d., or atenolol, 100 mg once a day, 50 mg of ICI 118551 t.i.d. failed to block beta 1-mediated inotropic stimulation and stimulation of renin by isoproterenol. We then performed a double-blind, placebo-controlled trial in patients with mild essential hypertension to compare this compound with propranolol, 80 mg t.i.d., and showed that ICI 118551 significantly decreased systolic and diastolic blood pressure. This antihypertensive effect was demonstrated by direct as well as by indirect blood pressure measurements. Thus, contrary to prevailing thought, beta 2-blockade has an antihypertensive effect independent of, and distinct from, beta 1-blockade.

Adrenergic beta-Antagonists↗