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Biomedical subjects

S G Ball

Publications and source records attributed to S G Ball.

At least 163 records · Page 9Linked to original sources
PubMed1988

Future approaches to the treatment of hypertension in the light of results from recent trials.

In this review approaches to the treatment of hypertension were appraised by considering data from recent trials. Two main questions were asked: at what level of blood pressure is treatment justified, and which drugs should be used? It is now well established that increases in both systolic and diastolic blood pressure are correlated with an increased risk of cardiovascular disease, heart attack or stroke. However, since patients are often asymptomatic, treatment must be justifiable in terms of reversing the risk of cardiovascular disease. The Australian Therapeutic Trial demonstrated that therapy was beneficial in patients whose diastolic pressure was at or above 95 mm Hg before treatment. Three recent large studies (EWPHE, IPPPSH and MRC) have provided interesting data on the level of blood pressure at which to start treatment and the most appropriate drugs to use. In one, treatment in the elderly, which raises particular concern, has been investigated. The MRC trial compared bendrofluazide with propranolol and showed a reduction in the incidence of stroke; however, to prevent 1 stroke, 850 patients would have to be treated for 1 year. Nevertheless, the benefits of therapy were clearly greater when diastolic blood pressure was at the upper end of the range 90-110 mmHg. Myocardial infarctions, which account for more deaths than stroke in mild to moderate hypertensives, do not appear to be reduced by treatment, whether or not this includes a beta-blocker. This is difficult to reconcile with the established 'cardioprotective' action of beta-blockers post-myocardial infarction. Other important factors affecting cardiovascular disease are governed by the patient's life-style, especially whether or not the patient smokes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular Disorders↗
PubMed1988

The effects of famotidine, 40 mg at night, on 24-hour intragastric acidity and plasma gastrin concentration in healthy subjects.

The effects of 40 mg oral famotidine at 2115 h on 24-h intragastric acidity and plasma gastrin concentration were measured in a double-blind placebo-controlled study in 10 healthy subjects. The subjects were studied on the 7th day of treatment with either famotidine or placebo. Famotidine, 40 mg at night, caused a pulse of decreased intragastric acidity during the night, with a longer-lasting elevation of plasma gastrin concentration. However, in the latter part of the day there was complete recovery from the antisecretory effects of the drug, with normal intragastric acidity and normal concentrations of plasma gastrin.

Adult↗
PubMed1988

Age-related effects of converting enzyme inhibitors: a commentary.

Experience with angiotensin converting enzyme (ACE) inhibitor drugs as with other antihypertensive agents, is limited in the elderly. Nevertheless, they appear effective and well tolerated but without evidence to suggest that they have any special role in the elderly compared to a younger age group. Most are excreted through the kidney and dosage should be reduced to match glomerular function. ACE inhibitors seem likely to be used increasingly in the elderly, especially when more traditional agents are contraindicated because of concomitant disease.

Aged↗
PubMed1987

Clinical pharmacology of ramipril.

Ramipril is a long-acting non-sulphydryl converting enzyme inhibitor that requires cleavage of its ester group to form the active diacid metabolite, ramiprilat. Renal excretion largely determines the drug's duration of action and the dosage should be reduced in patients with renal impairment. Oral ramipril given daily at dosages of 5 mg or more can control blood pressure over a 24-hour period; lower doses may be effective in patients with heart failure inadequately controlled by diuretics alone. No serious idiosyncratic adverse reactions have been reported. Ramipril is one of the most potent long-acting converting enzyme inhibitors developed; it is effective given once daily in the treatment of all grades of hypertension and of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Pharmacokinetics and effects on the renin-angiotensin system of ramipril in elderly patients.

Converting enzyme inhibitors are likely to be prescribed with increasing frequency in elderly patients. The pharmacokinetics of ramipril, a new potent long-acting non-sulphydryl converting enzyme inhibitor, and its effects on blood pressure, plasma renin activity and angiotensin II concentrations were studied in a group of 8 elderly volunteers (mean age 77, range 61 to 84). Circulating concentrations of the active diacid formed from its parent drug were consistently higher in this group despite apparently normal renal function, assessed by serum creatinine and urea concentrations, compared with younger volunteers (age range 21 to 30). The initial dose of ramipril should be lower in older subjects. The study emphasizes the importance of careful extrapolation of data obtained from young volunteers to older subjects.

Aged↗
PubMed1987

Plasma atrial natriuretic peptide concentrations during exercise in sodium replete and deplete normal man.

To explore the effects of exercise on plasma atrial natriuretic peptide (ANP) concentrations, eight normotensive volunteers performed maximal treadmill exercise in sodium replete and deplete states. Baseline immunoreactive plasma ANP concentrations were significantly lower during sodium depletion. During exercise plasma ANP rose in all subjects on both occasions. Plasma peptide responses were attenuated by sodium depletion with peak exercise levels only double baseline values, in contrast to the threefold increase in ANP concentrations observed when subjects were sodium replete. Plasma renin and aldosterone concentrations also rose with exercise. In contrast to changes in plasma ANP, the responses of both were enhanced by sodium depletion.

Adult↗
PubMed1987

Does dopamine regulate aldosterone secretion in the rat?

This study investigated the role of dopamine in the control of adrenal steroidogenesis. Adrenaline, noradrenaline and dopamine have been measured in plasma and in the adrenal zona glomerulosa and medulla of rats fed low, normal and high sodium diets and in zona glomerulosa tissue of rats with adrenal regeneration hypertension (ARH). Adrenal concentrations (means +/- SE) of adrenaline, noradrenaline and dopamine in rats fed a normal diet were 1471 +/- 335, 527 +/- 75 and 51 +/- 12 nmol/g in the medulla, and 66 +/- 17, 18 +/- 9 and 6 +/- 1 nmol/g in the zona glomerulosa. The dopamine content of the zona glomerulosa was greater than could be accounted for by simple contamination from the medullary catecholamines and is commensurate with that of tissue with dopaminergic innervation. Adrenal noradrenaline and adrenaline concentrations and plasma catecholamine and corticosterone concentrations were not affected by dietary sodium intake. Plasma aldosterone concentrations were greater than 3030.4, 339.8 +/- 41.5 and 55.2 +/- 11.0 pmol/l in rats fed low, normal and high sodium diets respectively. Five weeks after right adrenalectomy and nephrectomy and left adrenal enucleation, ARH rat systolic blood pressure had increased by 47 mmHg. In the regenerated gland, the concentrations of noradrenaline and adrenaline were negligible but dopamine was present in amounts similar to that of a normal adrenal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1987

Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes.

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.

Adolescent↗
PubMed1987

Diurnal change in plasma atrial natriuretic peptide concentrations.

1. Diurnal changes in plasma concentrations of atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, cortisol and antidiuretic hormone were investigated in seven normal volunteers studied under standardized conditions of dietary sodium, posture and physical activity. After completion of the diurnal study serial measurements of these variables were continued during, and on recovery from, a 2 day period of severe sodium depletion. 2. Clear diurnal variations in plasma concentrations of renin, angiotensin II, aldosterone, cortisol and antidiuretic hormone were observed. 3. Plasma ANP concentrations also varied significantly over 24 h. Values peaked about mid-day and a distinct trough in peptide concentrations occurred in the early evening. However, variations in plasma ANP values were of relatively small amplitude and not clearly independent of modest parallel shifts in sodium balance. 4. Changes in plasma ANP concentrations both within the diurnal study period and during sodium deprivation were closely and positively correlated with concomitant changes in cumulative sodium balance. 5. No simple parallel or reciprocal relationships between plasma concentrations of ANP, on the one hand, and concurrent plasma concentrations of other hormones or in the rate of urinary sodium excretion, on the other, were observed during the 25 h of the diurnal study.

Adult↗
PubMed1987

Converting enzyme inhibitors and the cardiovascular system.

Most commonly used drugs reduce blood pressure equally. Reduction in pressure lessens the chance of stroke but appears to have little impact on death from ischaemic heart disease in the majority. Loss of arterial compliance, development of cardiac hypertrophy, impaired coronary blood flow, and dysrhythmias may contribute, at least in part, to the adverse cardiac effects of hypertension. It is speculated that converting enzyme inhibitors could offer beneficial effects in these areas.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Clinical and biochemical effects of the renin inhibitor H142 in humans.

The inhibitor of human renin, H142, was studied in nine male volunteers. On three occasions, in random order, volunteers were infused with 5% dextrose, or with H142 at 1.0 or 2.5 mg/kg/h, for 30 min while supine and thereafter with dextrose for 1.5 h. There was a marked reduction in plasma active renin concentration as assayed by an enzyme-kinetic method, with parallel falls in the circulating concentrations of angiotensins (ANG) I and II, all of which rebounded transiently to values above basal after H142 infusion was stopped. In contrast, total renin concentration as measured by radioimmunoassay rose while ANG I and II fell, subsiding after H142 was discontinued. There was a slight but significant increase in plasma noradrenaline as renin became inhibited: plasma adrenaline was unchanged. H142 produced a slight fall in systolic blood pressure (SBP) and a clearer, highly significant, dose-related fall in diastolic blood pressure (DBP). There was modest but significant increase in the heart rate. These studies confirm H142 as an effective inhibitor of human renin in vivo.

Adult↗
PubMed1987

Dopamine affects angiotensin II-induced steroidogenesis by altering clearance of the peptide in man.

Infusion of dopamine is reported to reduce the response of aldosterone to infused angiotensin II in sodium-deplete but not sodium-replete man. Six normal male subjects were infused with angiotensin II in graded doses (2, 4 and 8 ng/kg per min) with or without dopamine (1.0 microgram/kg per min) during both dietary sodium repletion and depletion. The responses of both aldosterone and 18-hydroxycorticosterone to infusion of angiotensin II appeared to be reduced by dopamine in sodium-deplete, but not sodium-replete, subjects. However, when the relationships between plasma concentrations of angiotensin II and corticosteroid were examined it was evident that plasma concentrations of angiotensin II were lower when dopamine was infused concurrently with the peptide (P less than 0.05). In a second study, six sodium-deplete males were infused with angiotensin II at a constant rate (6 ng/kg per min) while dopamine (or placebo) was given in graded doses (0.5, 1 and 5 micrograms/kg per min). Renal plasma flow was estimated from total body clearance of para-aminohippuric acid. Overall, angiotensin II concentrations were lower during dopamine infusion compared with those during infusion of placebo (63.2 +/- 9.7 (S.E.M.) vs 92.3 +/- 6.4 pmol/l; P less than 0.01) and this was associated with a 40% increase in effective renal plasma flow (627 +/- 68 vs 451 +/- 15 ml/min; P less than 0.05); there again appeared to be a reduced aldosterone response during combined angiotensin II/dopamine infusion compared with that during infusion of angiotensin II alone (1003 +/- 404 vs 1225 +/- 146 pmol/l; 0.05 less than P less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxycorticosterone↗
PubMed1987

Antihypertensive mode of action of ketanserin.

The mechanism of blood pressure reduction by ketanserin in hypertensive patients is still not fully understood. It can occur in the absence of evident alpha 1-adrenergic blockade. However, particularly with prolonged therapy, features of alpha 1 blockade appear. There are both similarities and differences between the pattern of effects caused by ketanserin and prazosin. A central mode of action of ketanserin contributing to the blood pressure reduction is not excluded. It appears unlikely, however, that inhibition of aldosterone secretion makes a substantial contribution to the antihypertensive effect of ketanserin in humans.

Adrenergic alpha-Antagonists↗
PubMed1987

Does acute serotonergic type-2 antagonism reduce blood pressure? Comparative effects of single doses of ritanserin and ketanserin in essential hypertension.

We have studied the acute effects of the serotonergic type-2 (5-HT2) antagonists ketanserin and ritanserin given as single oral doses to patients with essential hypertension. Ketanserin has alpha 1-antagonist properties, whereas ritanserin is largely devoid of alpha 1-receptor binding affinity. Ketanserin (40 mg orally) caused a significant reduction (p less than 0.03) of sitting mean arterial pressure over the 8-h period following drug administration by an average of 15.4 +/- 3.2 mm Hg (mean +/- SEM) as compared to a reduction of 8.5 +/- 2.2 following placebo. In contrast, ritanserin had no significant effect on blood pressure compared to placebo; sitting mean arterial pressure was reduced by 9.0 +/- 2.6 and 10.8 +/- 1.8 mm Hg after administration of 10 and 20 mg, respectively, of ritanserin. There were no significant differences in pulse rate among placebo, ketanserin, or ritanserin phases. Ritanserin caused a reduction in the hostility score (p less than 0.05) as measured by the Multiple Affect Adjective Check List; ketanserin had no significant effects. The highly selective 5-HT2 antagonist ritanserin, given in a dose which caused measurable alteration of psychological function tests, had no acute effects on blood pressure. The acute antihypertensive effects of ketanserin are not caused by 5-HT2 antagonism alone, but are likely to be dependent on its alpha 1-antagonistic properties.

Adult↗
PubMed1987

Angiotensin converting enzyme inhibition in hypertension.

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Plasma alpha natriuretic peptide in cardiac impairment.

Regional plasma alpha human atrial natriuretic peptide concentrations were measured, and their relation to intracardiac pressures assessed, in an unselected series of 45 patients undergoing diagnostic cardiac catheterisation. Arteriovenous gradients in plasma concentrations of alpha human atrial natriuretic peptide were consistent with its cardiac secretion and its clearance by the liver and kidneys. Plasma concentrations of the peptide in the pulmonary artery, aorta, and superior vena cava correlated closely with the mean right atrial and pulmonary arterial pressures, and similar, though weaker, positive relations were seen with the left ventricular end diastolic and pulmonary artery wedge pressures. Concentrations of both atrial natriuretic peptide and renin showed significant inverse relations with serum sodium concentrations. Plasma concentrations of alpha human atrial natriuretic peptide are an additional objective indicator of the severity of haemodynamic compromise in patients with cardiac impairment.

Adolescent↗
PubMed1986

Molecular cloning and characterization of ARO7-OSM2, a single yeast gene necessary for chorismate mutase activity and growth in hypertonic medium.

The chorismate mutase structural gene, ARO7, which is necessary for both phenylalanine and tyrosine biosynthesis was cloned by complementation in yeast. Genetic analysis showed that ARO7 was identical to a gene necessary for growth in hypertonic medium, OSM2, which mapped nearby. After restriction mapping and subcloning of the plasmid, the cloned gene was used to detect mRNA levels in several growth conditions. Enzyme activities were measured in various genotypes. At our level of detection ARO7-OSM2 is a low level constitutively expressed gene.

Chorismate Mutase↗