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Biomedical subjects

G Jennings

Publications and source records attributed to G Jennings.

At least 127 records · Page 7Linked to original sources
PubMed1986

Brown adipose tissue thermogenesis during pregnancy in mice.

The thermogenic activity of interscapular brown adipose tissue has been assessed at different stages of pregnancy in mice. In late pregnancy there was a hypertrophy of the tissue which reversed at parturition. Neither the total protein content nor the total cytochrome oxidase activity of the tissue changed significantly throughout pregnancy or into early lactation (2-3 days, post-partum). However, mitochondrial GDP binding, an index of the activity of the proton conductance pathway, was significantly decreased at the end of pregnancy with a further decrease in early lactation. Moderate food restriction had no effect on either cytochrome oxidase activity or mitochondrial GDP binding at the end of pregnancy, as compared with pregnant animals fed ad libitum. Food restriction did, however, prevent the hypertrophy of brown adipose tissue in late pregnancy. It is concluded that brown adipose tissue thermogenesis is not significantly decreased in the pregnant mouse until shortly before parturition, even in animals subject to food restriction. It is also concluded that the normal dietary stimulation of thermogenesis in response to hyperphagia is suppressed in the pregnant animal.

Adipose Tissue, Brown↗
PubMed1986

The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity.

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p less than .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p less than .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p less than .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-density lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, but declined to sedentary levels with seven times per week exercise. Maximum oxygen uptake increased linearly with activity. Exercise performed three times per week lowers blood pressure and should reduce cardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure.

Adult↗
PubMed1986

Evidence for a predominantly central hypotensive effect of alpha-methyldopa in humans.

We examined the time course and extent to which central and peripheral mechanisms contribute to the short-term effects of a 500-mg oral dose of alpha-methyldopa on supine mean arterial pressure, cardiac output, and total peripheral resistance, as well as its effects on total urinary excretion of norepinephrine and its metabolites, in five subjects with essential hypertension. Total peripheral resistance was reduced significantly 1 hour after alpha-methyldopa administration and remained so for the ensuing 7 hours of the study (p less than 0.05). A small but significant reduction in mean arterial pressure occurred 7 hours after the dose (p less than 0.05), while cardiac output did not change significantly. Total 24-hour urinary norepinephrine and metabolite excretion was reduced by 8.1 mumol (35% compared with placebo). The relative distribution of urinary norepinephrine metabolites was unaffected by alpha-methyldopa, and the catecholamine metabolites of alpha-methyldopa, alpha-methylnorepinephrine and alpha-methylnormetanephrine did not account for this reduction. Competitive inhibition of methyldopa transport across the blood-brain barrier and into the central nervous system by large oral doses of isoleucine antagonized most of the effect of alpha-methyldopa. The effects on total peripheral resistance were completely abolished, and small, insignificant changes during the 7-hour study were similar to those observed after placebo. Changes in mean arterial pressure were not significant; however, 24-hour total urinary norepinephrine and metabolite excretion increased by 6.1 mumol to 22.7 mumol (24.7 mumol excreted after placebo). Adding benserazide to the alpha/methyldopa-isoleucine dose regimen in an attempt to inhibit any residual, presumably peripheral, effects of alpha-methyldopa caused little, if any, further antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Brown adipose tissue in patients with phaeochromocytoma.

Intra-abdominal adipose tissue was obtained at laparotomy from three subjects with high circulating noradrenaline concentrations in the presence of phaeochromocytoma. Light and electron microscopy confirmed typical brown adipose tissue, both adjacent to, and in one case distant from, the tumour. Biochemically, in terms of high cytochrome-C oxidase activity, mitochondrial GDP-binding, GDP-inhibitable uncoupled mitochondrial respiration, and specific concentration of uncoupling protein (mean 31 +/- 7 micrograms/mg mitochondrial protein) the tissue possessed all the unique features of thermogenically active brown adipose tissue. These findings are contrasted with low results obtained from a case with Cushing's disease, and the significantly lower results (mean 2.5 +/- 1.8 micrograms/mg) in a group of control adults (P less than 0.02). In the presence of high circulating noradrenaline concentrations, the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy, becomes reactivated and may be contributing to the weight loss which is typically seen with phaeochromocytoma. Human adult brown adipose tissue thus has the biochemical potential for the thermogenic activity required in order to contribute to the regulation of energy balance and body weight.

Adipose Tissue, Brown↗
PubMed1985

Measurement by radioimmunoassay of the mitochondrial uncoupling protein from brown adipose tissue of obese (ob/ob) mice and Zucker (fa/fa) rats at different ages.

The concentration of the 'uncoupling protein' in brown adipose tissue mitochondria has been measured in lean and obese (ob/ob) mice and Zucker (fa/fa) rats at different ages using a specific radioimmunoassay. During the suckling period the concentration of the protein was similar in normal and mutant animals of both types, despite the decrease in mitochondrial GDP binding observed in the obese. The concentration of uncoupling protein was, however, decreased in adult ob/ob mice and adult Zucker rats compared with their respective lean siblings, in parallel with the decrease in GDP binding. It is concluded that there is a 'masked', or inactive, form of uncoupling protein in young ob/ob mice and fa/fa rats.

Adaptation, Physiological↗
PubMed1985

Controlled trial of enalapril in congestive cardiac failure.

Twenty five patients with chronic congestive cardiac failure had enalapril (n = 13) or placebo (n = 12) added to their existing regimen of digoxin and frusemide in a randomised double blind trial. Four hours after the first 5 mg dose, the enalapril group showed significant falls in blood pressure, heart rate, and concentrations of plasma angiotensin II, angiotensin converting enzyme, and noradrenaline. During the 12 week trial heart failure became worse in one enalapril treated patient (8%) and in seven placebo treated patients (58%). There were no significant changes in cardiac ejection fraction or exercise duration in either group. Plasma noradrenaline response to graded exercise and maximum exercise rate-pressure product were significantly reduced after four and 12 weeks of active treatment but unchanged with placebo treatment. There was a sustained increase in plasma potassium and a slight rise in plasma creatinine in the enalapril group. Plasma concentrations of the active drug, enalaprilate, were dose related and log enalaprilate correlated significantly with percentage of plasma angiotensin converting enzyme activity (r = -0.66). Enalapril was well tolerated and produced no adverse effects. The drug appears to be superior to placebo and offers considerable promise for the treatment of this condition.

Angiotensin II↗
PubMed1984

Enalapril for severe congestive heart failure. A double-blind study.

The effects of the new, orally administered converting-enzyme inhibitor, enalapril (MK-421), were studied in 12 ambulatory patients with severe cardiac failure who were also receiving digoxin and diuretic agents. The study was double-blind, parallel, placebo-controlled and randomized. The clinical characteristics and pretreatment exercise performance were similar in the two groups of patients. All vasodilator drugs had been withdrawn two weeks before the start of the trial. At 12 weeks, the patients receiving enalapril showed a significant improvement in the functional class of the disease, exercise time (P less than 0.01), and maximum workload achieved, and experienced relief of symptoms. Blood pressure fell in patients receiving active treatment suggesting a reduction of afterload. Left ventricular ejection fraction was unchanged in enalapril-treated patients, but fell in patients on placebo (P less than 0.001). Enalapril was well tolerated without apparent adverse effects. It was effective when used with digoxin and diuretic agents in the treatment of severe cardiac failure, and its efficacy was maintained throughout 12 weeks of therapy.

Administration, Oral↗
PubMed1984

Plasma noradrenaline kinetics in humans.

Recently developed radiotracer methods for measuring the overall rate of release of noradrenaline to plasma, for the body as a whole, can be used to estimate 'total sympathetic nervous system activity' in humans. These techniques find application in clinical studies of sympathetic nervous physiology and pharmacology. The inherent weakness of any biochemical test of global sympathetic tone such as this lies in the fact that sympathetic nervous system responses typically show regional differentiation. Biochemical indices of overall sympathetic activity are insufficiently discriminating to delineate patterns of sympathetic nervous response, representing instead an algebraic sum of all regional increases or decreases in sympathetic tone. Modification of the whole-body radiotracer methodology enables organ-specific sympathetic nervous system activity to be estimated, from measurements of regional release of noradrenaline to plasma. This should facilitate investigation of possible sympathetic pathophysiology in disease states. Illustrative of potential application of the method are preliminary findings of increased renal sympathetic nervous tone in young patients with essential hypertension, and of selective activation of sympathetic nerves to the kidney by diuretics.

Humans↗
PubMed1984

Cardioselectivity, kinetics, hemodynamics, and metabolic effects of xamoterol.

Xamoterol is a new orally active partial beta-adrenoceptor agonist. Its kinetics, hemodynamic and metabolic effects, and cardioselectivity were investigated in eight normal subjects. Plasma xamoterol concentrations after 100 micrograms/kg iv declined biexponentially over 8 hr and t 1/2 beta averaged 2.6 hr. Resting heart rate (HR) increased slightly in the supine position but was unchanged on sitting. Systolic blood pressure (SBP) rose by 5 to 10 mm Hg and cardiac index (CI) rose 15% to 20%. Both parameters were above control values 6 hr after dosing, when plasma xamoterol concentrations had fallen to about 10 ng/ml. There were no changes in diastolic or mean arterial pressure (MAP). During graded exercise the effects of xamoterol on HR and SBP were the reverse of those at rest, with lowering of exercise HR and SBP at higher work loads. CI during exercise was not altered by xamoterol. Doses of xamoterol were calculated from the kinetic data to give plasma concentrations of 100, 200, 400, and 800 ng/ml. HR and blood pressure effects at each xamoterol level were compared before and after inhibition of cardiovascular reflexes with prazosin, atropine, and clonidine. Hemodynamic effects of xamoterol and isoproterenol were compared. Before autonomic block xamoterol increased HR by 10 bpm and MAP by 7 mm Hg at the highest dose. After autonomic block there was a 200% to 300% rise in HR at each dose and MAP still rose. The rise in MAP after block could be entirely accounted for by a 23% increase in CI because total peripheral resistance did not change. The effects of isoproterenol after autonomic block were a rise in HR and a fall in MAP. Metabolic responses to xamoterol were measured at the four dose levels. There was a dose-related increase in nonesterified fatty acids and a fall in plasma lactate levels but no changes in plasma renin activity or blood glucose. Results suggest that xamoterol is a cardioselective partial beta-adrenoceptor agonist in man.

Adrenergic beta-Agonists↗
PubMed1984

Two patients with abnormalities of regional sympathetic nervous tone.

The traditional biochemical tests of sympathetic nervous system function used in clinical diagnosis (urine and plasma catecholamine measurements) are indices of "overall" sympathetic nervous activity, and incapable of detecting localised changes in sympathetic tone confined to individual organs. Recently developed radiotracer methods, which enable the pattern of sympathetic nervous dysfunction in disease states to be delineated, were used to detect abnormalities in regional sympathetic nervous system activity in two patients presenting problems in management. In one, the abnormality of sympathetic function was iatrogenic, a post-sympathectomy denervation of the lower regions of the body, associated with incapacitating postural hypotension. In the other, unexplained persistent sinus tachycardia proved to be due to an increase in sympathetic nervous tone restricted to the innervation of the heart. Knowledge of the underlying sympathetic nervous pathophysiology in these patients influenced the choice of drugs subsequently used in their treatment.

Dihydroergotamine↗
PubMed1984

Measurement of total and organ-specific norepinephrine kinetics in humans.

A variety of biochemical tests, most notably measurement of the plasma concentration of norepinephrine, have been used to quantify overall sympathetic nervous system activity in humans. Plasma norepinephrine values provide a fallible index of sympathetic activity in that they are dependent in part on the rate of removal of norepinephrine from plasma. Measurement of the rate of release of norepinephrine to plasma is a better guide to overall sympathetic nervous tone because it avoids this confounding influence of norepinephrine plasma clearance. The overall norepinephrine spillover measurement, however, suffers from one major limitation: the sources of the released norepinephrine are not identified. Recently developed radiotracer techniques allow the estimation of regional sympathetic nervous activity from measurements of the organ-specific norepinephrine spillover rate. We find that the lungs are the main source of norepinephrine release to plasma, with mean pulmonary norepinephrine spillover of 159 ng/min constituting 40% of total norepinephrine release. Pulmonary norepinephrine release exceeded the combined norepinephrine spillover from the heart (3%), kidneys (17%), and hepatomesenteric circulation (8%).

Humans↗
PubMed1984

Redevelopment of essential hypertension after cessation of long term therapy; preliminary findings.

We have previously found that the vascular hypertrophy that accounts for the maintenance of a substantial fraction of the elevation of the total peripheral resistance index (TPRI) in essential hypertension can be almost completely reversed by one years antihypertensive treatment (1). On ceasing treatment, blood pressure returns rapidly to pretreatment values suggesting that the original cause of the hypertension is still present. In the present study, 7 patients stopped a standard regimen for 10 weeks after at least 2 years of normotension. In the first week, standing and lying blood pressure increased related to rise in supine cardiac index and TPRI. Thereafter standing pressures, supine systolic blood pressure and cardiac index (CI) increased further, but supine diastolic blood pressure and TPRI did not alter. Changes in measurements of resting sympathetic activity, plasma volume or renin-angiotensin did not account for these observations. The return of hypertension after stopping effective therapy has some features previously described in borderline hypertension, particularly increasing systolic blood pressure, CI and postural blood pressure responses. Some of the changes may reflect the relative preponderance of cardiac and vascular amplifiers.

Blood Pressure↗
PubMed1984

Total, and organ-specific, noradrenaline plasma kinetics in essential hypertension.

We have developed radiotracer techniques, based on measurement of the rate of spillover of noradrenaline to plasma, to simultaneously estimate total, and organ-specific, sympathetic nervous activity in humans. In 27 unmedicated subjects without renal or liver disease, or cardiac failure, regional noradrenaline spillover rates were as follows: lungs 33% of total noradrenaline release to plasma, kidneys 22%, skeletal muscle 20%, hepatomesenteric 9%, skin 5%, and heart 3%. These findings have relevance to numerous previous studies on the importance of the sympathetic nervous system in the pathogenesis of human essential hypertension. The indices of overall sympathetic nervous tone which have been used, such as measurements of plasma noradrenaline concentration or total NA release to plasma, are seen to be not sufficiently specific, since the organs and regions thought to be central to hypertension pathogenesis (kidney, heart, splanchnic circulation) are responsible for no more than 35% of all noradrenaline released to plasma. Organ-specific noradrenaline spillover measurements are better suited to the elucidation of any sympathetic nervous system pathophysiology in human hypertension. Early results point to an increase in renal sympathetic tone in young patients with essential hypertension.

Humans↗
PubMed1984

Contribution of individual organs to total noradrenaline release in humans.

Plasma noradrenaline measurements are a fallible guide to sympathetic nervous tone, being dependent on noradrenaline plasma clearance. We have developed radiotracer techniques, based on measurement of the rate of spillover of noradrenaline to plasma, to simultaneously estimate total, and organ-specific, sympathetic nervous activity in humans. In 27 unmedicated subjects without renal or liver disease, or cardiac failure, regional noradrenaline spillover rates were as follows: lungs 138 +/- 36 ng/min (mean +/- SE) (33% of total noradrenaline spillover), kidneys 77 +/- 10 ng/min (22% of total), skeletal muscle 64 +/- 11 ng/min (20%), hepatomesenteric 29 +/- 9 ng/min (9%), skin 18 +/- 4 ng/min (5%), and heart 11 +/- 4 ng/min (3%). Organ-specific noradrenaline spillover measurements are well suited to the elucidation of sympathetic nervous system pathophysiology in human diseases. Since the sympathetic nervous system outflow to individual organs is not activated or suppressed uniformly in different disease states, biochemical measures of "overall sympathetic nervous activity" are insufficiently specific for this purpose.

Humans↗
PubMed1983

Effect of acclimation temperature on the concentration of the mitochondrial 'uncoupling' protein measured by radioimmunoassay in mouse brown adipose tissue.

The effect of acclimation temperature on the concentration of the mitochondrial 'uncoupling' protein (Mr 32000) from brown adipose tissue of mice has been investigated. The uncoupling protein was measured by a specific radioimmunoassay. Between 33 degrees C (thermoneutrality) and -2 degrees C there was a progressive increase with decreasing environmental temperature in the amount of uncoupling protein. For mice at -2 degrees C the mitochondrial concentration of the protein was 9-times higher than at 33 degrees C, while the total amount of the protein in interscapular brown adipose tissue was estimated to be nearly 80-times greater at -2 degrees C compared to 33 degrees C.

Acclimatization↗
PubMed1983

Electrolyte metabolism in patients with periodic affective disorders during treatment with rubidium.

Five patients suffering from periodic affective disorders with short mood-cycles were treated with rubidium chloride, producing peak erythrocyte concentrations between 9 and 13 mmol/l. Loading with rubidium was associated with decreased total body potassium, but red-cell potassium was unchanged. Regular mood-cycling was disturbed, together with the associated body-weight changes. There was a slight extracellular "metabolic" acidosis. Electrolyte concentrations fluctuate abnormally in these patients, and two muscle biopsy specimens had very low potassium contents.

Affective Disorders, Psychotic↗