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Biomedical subjects

G Jennings

Publications and source records attributed to G Jennings.

At least 109 records · Page 6Linked to original sources

Measurement of overall and cardiac norepinephrine release into plasma during cognitive challenge.

Measurements of plasma norepinephrine concentrations and norepinephrine spillover into plasma were used to gauge sympathetic nervous system activation during cognitive challenge (forced mental arithmetic) in 12 human subjects. Norepinephrine levels were influenced by the sampling site, with the fractional increase being greatest for norepinephrine spillover from the heart (where norepinephrine release almost trebled), intermediate for the arterial plasma norepinephrine concentration and total body norepinephrine spillover (50-70% increase), and inconsequential for antecubital venous plasma norepinephrine levels (less than 20% increase). These findings are explained by patterning of the sympathetic response, which only minimally involves the sympathetic outflow to the skeletal muscle of the forearm but preferentially involves the heart. Antecubital venous plasma norepinephrine levels are not sufficiently sensitive to allow satisfactory monitoring of the sympathetic neural outflow to organs, such as the heart, which are selectively activated in the response to mental challenge.

Adult↗

Noradrenaline release and the pathophysiology of primary human hypertension.

Measurements of the overflow of norepinephrine to plasma from individual organs (using radiotracer methodology) were used to delineate the pattern of sympathetic nervous system activation present in primary human hypertension. Mean total norepinephrine (NE) spillover in hypertensive patients was 418 ng/min, 42% (124 ng/min) higher than in subjects with normal blood pressure (BP)(P less than .05). Norepinephrine spillover among hypertensive patients was a function of age, only being elevated in patients under 40 years of age. Half of the excess in total norepinephrine release in hypertensive patients was accounted for by increased cardiorenal spillover. Mean renal norepinephrine spillover was 120 ng/min, compared with 69 ng/min in healthy subjects (P less than .02). Renal spillover was highest in younger patients. Corresponding cardiac norepinephrine spillover values were 12.6 ng/min and 5.1 ng/min (P less than .01). The balance of the excess total norepinephrine spillover comes from undetermined sites, but not the lungs or hepatomesenteric circulation. These measurements of regional norepinephrine overflow suggest that sympathetic nervous outflow to the kidneys and heart is selectively activated in early hypertension.

Humans↗

Brown adipose tissue activity in pyrexial cases of cot death.

Brown adipose tissue was investigated in two cases of cot death in which core temperatures were above 40 degrees C on arrival at the mortuary. Evidence was obtained from mitochondrial (8-3H) guanosine diphosphate (GDP) binding and oxygen uptake of active thermogenesis with uncoupled mitochondrial respiration which was recoupled by GDP. Thermogenic capacity of brown adipose tissue, estimated by radioimmunoassay of the specific mitochondrial membrane "uncoupling protein" responsible for heat production, was similar to that measured in other infants or in experimental animals acclimated to moderately warm conditions (23 degrees C). Brown adipose tissue thermogenesis, occurring inappropriately in a warm, well insulated infant, could be a cause of some cases of cot death.

Adipose Tissue, Brown↗

Regional norepinephrine turnover in human hypertension.

Overall and regional rates of norepinephrine overflow to plasma were measured in 55 untreated patients with primary hypertension and in 40 healthy subjects, to study sympathetic nervous pathophysiology in human hypertension. Total norepinephrine spillover was increased in primary hypertension, particularly in patients aged less than 40 years, largely due to higher rates of renal and cardiac norepinephrine overflow. Renal renin release, and arterial plasma renin activity, were highest in these younger patients with increased renal sympathetic nervous activity. In older patients sympathetic activity and norepinephrine release was typically normal. A selective increase in the sympathetic nervous outflow to the heart and kidneys is commonly present in young patients with primary hypertension, and probably contributes materially to the early pathogenesis of the hypertension.

Female↗

Nonshivering thermogenesis and the thermogenic capacity of brown fat in fasted and/or refed mice.

The effects of fasting and refeeding on nonshivering thermogenesis and the properties of brown adipose tissue have been investigated in mice. Fasting for 48 h led to a substantial reduction in the capacity for nonshivering thermogenesis, and there was no recovery of thermogenic capacity during the first 5 days of refeeding. A period of 10-15 days of refeeding was required for full restoration of thermogenic capacity. The mice were hyperphagic during the first 6 days of refeeding, but body weight was recovered after 24 h. The amount of interscapular brown adipose tissue decreased substantially on fasting, but it recovered 24 h after the initiation of refeeding. Cytochrome oxidase activity, the level of mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein in brown adipose tissue were each reduced by fasting. Although both GDP binding and the specific concentration of uncoupling protein rapidly returned to normal on refeeding, the activity of cytochrome oxidase was not normalized until 10 days after the end of the fast. These results indicate that a prolonged period of refeeding is required for the recovery in the capacity for nonshivering thermogenesis following a fast, a similar time course being evident for the recovery of cytochrome oxidase activity in brown adipose tissue. It is suggested that the fasting-induced reduction in the capacity for nonshivering thermogenesis is linked primarily to a loss of mitochondria from brown adipose tissue and that the normalization of thermogenic capacity is dependent on the restoration of mitochondrial mass.

Adipose Tissue, Brown↗

Functional atrophy of brown adipose tissue during lactation in mice. Effects of lactation and weaning on mitochondrial GDP binding and uncoupling protein.

The thermogenic activity and capacity of brown adipose tissue were determined in mice during lactation and after weaning. There was a marked fall during lactation in the mitochondrial content of the tissue, and in GDP binding and the specific mitochondrial concentration of uncoupling protein. The lactation-induced functional atrophy of brown adipose tissue was fully reversible after weaning; mitochondrial content and the mitochondrial concentration of uncoupling protein were both restored, although GDP binding was not normalized.

Adipose Tissue, Brown↗

Effect of E. coli endotoxin on temperature, oxygen consumption and brown adipose tissue thermogenesis in rats and mice.

The effects of E. coli endotoxin 0127 B8 on oxygen consumption, temperature, and on the activity of the proton conductance pathway in brown adipose tissue (BAT) were investigated in rats and mice. In rats an increase was observed in rectal and skin temperature, whole body oxygen consumption and GDP binding in BAT. In mice only the rise in rectal and skin temperature were significantly changed by endotoxin administration. These findings suggest that in some species BAT is involved in the production of endotoxin induced fever and increased energy expenditure.

Adipose Tissue, Brown↗

Effect of warm or cold exposure on GDP binding and uncoupling protein in rat brown fat.

The effects of acute and chronic exposure to different environmental temperatures on the total tissue cytochrome oxidase activity, level of mitochondrial GDP binding, and specific mitochondrial concentration of uncoupling protein have been investigated in rat brown adipose tissue, a radioimmunoassay being used to measure uncoupling protein. Acclimation at different temperatures for 3 wk produced parallel changes in GDP binding, the concentration of uncoupling protein, and the activity of cytochrome oxidase, each parameter rising with decreasing temperature between thermoneutrality (29 degrees C) and 4 degrees C. Acute exposure of warm-acclimated (29 degrees C) rats to the cold (4 degrees C) led to a rapid increase in GDP binding without any alteration in the amount of uncoupling protein. The increase in binding was accompanied by an increase in the rate of acetate-induced swelling of the mitochondria. The concentration of uncoupling protein in warm-acclimated rats was significantly raised only after 48 h exposure to cold. When cold-acclimated rats were exposed acutely to the warm, there was a rapid decrease in GDP binding without any alteration in the amount of uncoupling protein. It is concluded that after alterations in environmental temperature the concentration of uncoupling protein in brown adipose tissue mitochondria changes much more slowly than GDP binding and that binding can therefore be dissociated from the amount of the protein.

Acclimatization↗

The place of exercise in the long-term treatment of hypertension.

The antihypertensive effects of exercise have been examined in 2 randomized studies of multiple levels of activity. In 12 normal subjects, 1 month's exercise 3 times weekly lowered blood pressure (BP) and vascular resistance. There was only a slightly greater effect after 7 times/week exercise. In most subjects there was a marked reduction in noradrenaline spillover rate, a measure of sympathetic activity. Exercise also improved glucose utilization and lowered plasma cholesterol. Thirteen previously untreated patients with essential hypertension had an average fall in BP of 11/9 and 16/11 mm Hg after 1 month each of 3/week and 7/week exercise respectively, again associated with fall in vascular resistance and a 20-30% reduction in plasma noradrenaline. BP remained lowered by 3/week exercise for 1 year. In patients who had BP controlled with drug for greater than 1 year, exercise 3 times weekly also prevented the redevelopment of hypertension after long-term drug therapy was ceased. Regular exercise is useful in the initial management of patients with mild hypertension. In more severely hypertensive patients, exercise may also be effective after an initial period of drug therapy.

Blood Pressure↗

Sympathetic tone modulates portal venous pressure in alcoholic cirrhosis.

Sixteen alcoholic cirrhotic patients with portal hypertension were studied before and after 2.5 micrograms/kg intravenous clonidine. In six patients portal venous pressure was assessed simultaneously by wedged hepatic vein and transhepatic portal vein cannulation. Wedged hepatic vein pressure accurately reflected portal venous pressure both before and after clonidine (r = 0.912 and 0.940; p less than 0.01). In all the other ten patients, sympathetic tone, measured by total plasma noradrenaline spillover, was high (755 +/- 123 ng/min; normal 296 +/- 29 ng/min). It fell significantly after clonidine (378 +/- 95 ng/min; p less than 0.01). This fall was associated with a decrease in corrected wedged hepatic vein pressure (18.6 +/- 1.1 to 13.4 +/- 0.5 mm Hg; p less than 0.01) but no change in estimated hepatic blood flow (934 +/- 94 to 976 +/- 102 ml/min), indicating a fall in postsinusoidal hepatic vascular outflow resistance. Clonidine-induced changes in mean arterial pressure and cardiac output were independent of the change in portal venous pressure. The results suggest that in alcoholic cirrhosis there is a labile component of hepatic vascular resistance which is partly under sympathetic nervous control and is thus potentially sensitive to pharmacological control.

Adult↗

Evidence that fasting can induce a selective loss of uncoupling protein from brown adipose tissue mitochondria of mice.

The effects of fasting and refeeding on the concentration of uncoupling protein in brown adipose tissue mitochondria have been investigated in mice. Fasting mice for 48 h led to a large decrease in the total cytochrome oxidase activity of the interscapular brown fat pad. Mitochondrial GDP binding and the specific mitochondrial concentration of uncoupling protein also fell on fasting. After 24 h refeeding both GDP binding and the mitochondrial concentration of uncoupling protein were normalized, but there was no alteration in the total tissue cytochrome oxidase activity. Fasting appears to induce a selective loss of uncoupling protein from brown adipose tissue mitochondria, which is rapidly reversible on refeeding.

Adipose Tissue, Brown↗

Effect of caging singly or in groups of different sizes on the thermogenic activity of interscapular brown adipose tissue in mice.

The effects on the thermogenic activity of brown adipose tissue of caging mice singly or in groups of different sizes has been investigated. At 23 degrees C the total cytochrome oxidase activity and the level of mitochondrial GDP binding were higher in mice caged singly than in mice caged in groups of three or six. At 4 degrees C GDP binding and cytochrome oxidase activity were lower in mice caged in groups of two, three or six than in mice caged singly. The mitochondrial concentration of uncoupling protein was not clearly affected by the number of mice in each cage.

Adipose Tissue, Brown↗

Brown adipose tissue uncoupling protein content in human infants, children and adults.

A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity. The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly. The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue. Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects. Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children.

Adipose Tissue, Brown↗

Mechanism of elevated plasma noradrenaline in the course of essential hypertension.

Increased sympathetic nervous system tone may be the initiating pathophysiologic event in some patients with essential hypertension. We estimated sympathetic nervous activity from radiotracer-derived measurements of noradrenaline release to plasma in 34 patients with essential hypertension and 23 subjects with normal blood pressure. The plasma concentration of noradrenaline (32% increased) and the rate of release of noradrenaline to plasma (38% increased) were elevated overall in patients with essential hypertension, largely due to higher noradrenaline release in hypertensive patients aged less than 40 years. Noradrenaline release from the kidneys and heart was elevated; renal noradrenaline spillover was 2.4 times normal in patients aged less than 40 years. Increased renal noradrenaline spillover accounted for 42% and increased cardiac noradrenaline spillover for 4% of the excess total noradrenaline spillover in essential hypertension, leaving 54% unexplained. Total noradrenaline spillover to plasma was normal in hypertensive patients aged 60 years and over. The plasma noradrenaline concentration was similar in younger and older hypertensive patients, despite lower noradrenaline release in the latter due to an age-dependent fall in noradrenaline plasma clearance in essential hypertension. Cardiorenal sympathetic nervous system tone appears to be increased in essential hypertension, particularly in younger patients. This contributes substantially to the higher plasma noradrenaline values found.

Adult↗

Echocardiographic measurement of left ventricular hypertrophy in untreated essential hypertension.

The prevalence of left ventricular hypertrophy (LVH) in human essential hypertension is uncertain. Echocardiography was used to calculate left ventricular wall thickness (WT), relative wall thickness (t/r) and left ventricular mass (LVM) in 52 normal subjects, 30 patients with borderline hypertension and 33 untreated patients with essential hypertension. In 52 normal subjects WT was independent of age, sex, BSA, BP or habitual physical activity, but LVM was significantly related to BSA and age. After correction of LVM for age and BSA, 88% of 33 patients with untreated essential hypertension had LVM greater than predicted which identified a larger proportion of hypertensives with LVH than previous studies suggest. Wall thickness measurement alone also indicated that about 80% of newly diagnosed hypertensives have LVH.

Adolescent↗

Energy balance and brown adipose tissue thermogenesis during pregnancy in Syrian hamsters.

Energy balance and brown adipose tissue thermogenesis were examined during pregnancy in Syrian hamsters (Mesocricetus auratus). Neither estrous cycles nor pregnancy had any effect on food intake, but both were accompanied by significant changes in body weight. Despite their substantial weight gains (attributable to growth of fetuses and placentas), pregnant hamsters actually lost a mean of 48 kJ in carcass energy, whereas unmated controls gained 98 kJ over the same 15 days. During pregnancy hamsters exhibited an increase in protein deposition (almost entirely in the fetuses and placentas), but they lost nearly 40% of their body lipid. An apparent increase in energy expenditure occurred despite a highly significant decrease in brown adipose tissue thermogenesis during pregnancy. By day 15 of pregnancy (within 13 h of expected parturition) there were substantial decreases in interscapular brown adipose tissue weight (-59%), protein content (-54%), and cytochrome-c oxidase activity (-69%). These changes in brown adipose tissue were evident by day 4 of pregnancy and persisted through lactation. It is suggested that this suppression of brown adipose tissue function is due to increased circulating levels of prolactin and subsequently to the nutritional stress of conceptus growth in the absence of an increase in food intake.

Adipose Tissue, Brown↗