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Biomedical subjects

L Landsberg

Publications and source records attributed to L Landsberg.

At least 91 records · Page 5Linked to original sources
PubMed1984

Dissociation of sympathetic nervous system and adrenal medullary responses.

The relative importance of sympathetic nerve (SNS) activity and adrenal medullary secretion in various physiological situations has generally been inferred from measurements of norepinephrine (NE) and epinephrine (E), respectively, in urine or plasma. Increasing evidence, however, indicates that under certain conditions the adrenal medulla may release substantial amounts of NE as well as E. In several of these circumstances, estimates of SNS activity based on the measurement of NE turnover in peripheral tissues of experimental animals indicate diminished SNS function, a reduction that is independent of adrenal medullary secretion. These reciprocal alterations in SNS and adrenal medullary activity fall into two patterns. First, when SNS activity is suppressed by fasting, adrenal medullary responses to various stimuli are enhanced. Second, for certain stimuli the SNS response is biphasic, with an initial suppression followed by subsequent stimulation; during the first phase adrenal medullary secretion is markedly increased. The physiological contribution of the adrenal medulla, therefore, would be particularly important under conditions of SNS suppression.

Adrenal Medulla↗
PubMed1984

Sympathoadrenal system and regulation of thermogenesis.

The sympathetic nervous system (SNS) plays a critical role in the regulation of mammalian thermogenic responses to cold exposure and dietary intake. Catecholamine-stimulated thermogenesis is mediated by the beta-adrenergic receptor. In the rat brown adipose tissue is the major site of metabolic heat production in response to both cold (nonshivering thermogenesis) and diet (diet-induced thermogenesis). Measurements of norepinephrine turnover rate in interscapular brown adipose tissue of the rat demonstrate increased sympathetic activity in response to both cold exposure and overfeeding. In adult humans, a physiologically significant role for brown adipose tissue has not been established but cannot be excluded. It appears likely that dietary changes in SNS activity are related, at least in part, to the changes in metabolic rate that occur in association with changes in dietary intake.

Adipose Tissue, Brown↗
PubMed1983

Sympathetic nervous system and adrenal medullary responses to ischemic injury in mice.

Acute, severe injury is frequently attended by hypotension, hypothermia, and decreased metabolic rate despite elevated urine and plasma catecholamine levels. Because the combination of sympathetic nervous system (SNS) suppression and adrenal medullary stimulation documented in several other situations could account for these observations, SNS and adrenal medullary function were examined independently in mice in the hindlimb ischemia model of acute injury. SNS activity was assessed by the measurement of [3H]norepinephrine (NE) turnover in heart and adrenal medullary secretion by depletion of adrenal catecholamine content. In nine separate experiments during the first 10 h after termination of a 2.5-h period of hindlimb ischemia, cardiac NE turnover was reduced an average of 23% (P less than 0.05) in injured mice. At the same time, adrenal catecholamine content fell 37% (P less than 0.05) in injured animals but not in controls. In contrast to the acute reaction, SNS activity in mice surviving 3 days was 59% greater than in controls. Thus, the reduction in NE turnover and depletion of adrenal catecholamine content suggest that SNS suppression and adrenal medullary stimulation constitute the acute sympathoadrenal response in this model of severe injury. Because survival within the first 24 h after injury was decreased in adrenalectomized mice despite glucocorticoid treatment, adrenal medullary catecholamines may contribute to survival in severely injured animals. Furthermore, because the SNS plays an important role in the regulation of blood pressure and heat production, the diminution in SNS activity in the hours after injury may contribute to posttraumatic hypotension and hypometabolism.

Adrenal Medulla↗
PubMed1983

Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse.

The genetically obese (ob/ob) mouse exhibits defective thermoregulatory responses to cold exposure. Pathophysiological explanations for this phenomenon have focused on abnormalities in intracellular metabolism or insensitivity of peripheral tissues to the thermogenic effects of catecholamines. Because the sympathetic nervous system (SNS) is subject to feedback regulation, a peripheral impairment in thermogenesis should be associated with a compensatory increase in SNS activity. To examine SNS activity in the ob/ob mouse, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of ob/ob and lean mice. The results from studies utilizing radiolabeled NE or inhibition of NE biosynthesis with alpha-methyl-p-tyrosine to measure NE turnover demonstrated reductions in SNS activity of 33-56% in heart and of 45-73% in IBAT in ob/ob mice at ambient temperature (22 degrees C) compared with measurements in lean controls. During cold exposure (4 degrees C) NE turnover increased in heart and IBAT to a similar extent in both ob/ob and lean mice, but NE turnover rates in heart, and probably in IBAT as well, remained lower in the obese mice than in the lean despite the gradual development of hypothermia in the ob/ob mice during this period. Administration of naltrexone, a long-acting opiate antagonist, failed to reverse the suppression of SNS activity observed in the ob/ob mice. These data indicate that diminished SNS activity in ob/ob mice may be an additional factor contributing to the defective thermogenesis characteristic of these animals.

Adipose Tissue, Brown↗
PubMed1983

Sympathoadrenal responses to acute and chronic hypoxia in the rat.

The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla.

Adrenal Medulla↗
PubMed1983

Effect of dietary fat on sympathetic nervous system activity in the rat.

Previous studies from our laboratory have demonstrated that dietary intake affects the sympathetic nervous system (SNS); carbohydrate intake, in particular, has been shown to stimulate sympathetic activity. The present studies were undertaken to characterize the effect of dietary fat on SNS activity in the rat. Sympathetic activity was assessed by measurement of norepinephrine (NE) turnover in heart, interscapular brown adipose tissue (IBAT), and pancreas and by excretion of NE in the urine. When fed a fat-enriched diet (50% chow, 50% lard), fractional NE turnover in heart (k) increased from 6.3 +/- 0.6% h in ad lib. fed controls to 14.7 +/- 1.3% h in the high-fat group (P less than 0.001); calculated NE turnover rate increased from 24.5 +/- 2.4 ng/heart per h to 36.8 +/- 3.5 (P less than 0.05). Urinary NE excretion more than doubled after 6 d of the same high fat diet (P less than 0.001). Ganglionic blockade produced a greater effect on NE turnover in fat-fed, as compared with chow-fed animals, consistent with increased sympathetic activity in the fat-fed group. When fat absorption was blocked with a bile acid binding resin (cholestyramine), the same high-fat diet did not increase cardiac NE turnover, indicating that fat absorption is required for the stimulatory effect on sympathetic activity. In another series of experiments, in which chow (and hence protein) intake was held constant, the effect of fat and isocaloric sucrose supplements on NE turnover was assessed in heart, IBAT, and pancreas. The caloric value of the supplements was 50, 100, and 335% of the chow in the different experiments. An effect of fat on NE turnover in heart and IBAT was demonstrable at the lowest level of fat supplement. Fat increased pancreatic NE turnover when added in amounts sufficient to double the caloric intake. The stimulatory effect of sucrose and fat on NE turnover in heart and IBAT was similar. These experiments demonstrate that fat increases SNS activity in the rat and that the magnitude of the effect is similar to that of sucrose. The results imply that fat may contribute to dietary thermogenesis in this species.

Adipose Tissue, Brown↗
PubMed1982

Restricted food intake limits brown adipose tissue hypertrophy in cold exposure.

Two factors that may determine brown adipose tissue (BAT) hypertrophy during conditions of increased metabolic heat production are increased food intake and increased sympathetic nervous system (SNS) activity. Since these two proceed pari passu during cold exposure, their independent contributions to BAT hypertrophy are unknown. To examine the role of each, we limited the food intake of a group of cold exposed rats by pair feeding them to warm exposed control rats and then compared the pair fed rats to ad lib fed cold exposed animals. Restricted food intake limited absolute BAT hypertrophy (0.226 +/- 0.01 g. vs 0.488 +/- 0.02 g, pair fed vs ad lib, P less than 0.01), BAT as per cent body weight (0.189 +/- 0.12 vs 0.252 +/- 0.012, P less than 0.01) and BAT protein content (34.4 +/- 3.8 vs 48.9 +/- 2.6 mg, P less than 0.01) despite evidence of quantitatively similar activation of the SNS in BAT in both groups. We conclude that increased food intake contributes to BAT hypertrophy in cold exposure independent of sympathetic activity.

Adipose Tissue, Brown↗
PubMed1982

Diet-induced changes in sympathetic nervous system activity: possible implications for obesity and hypertension.

The sympathetic nervous system responds to changes in caloric intake; caloric restriction decreases and carbohydrate administration increases sympathetic nervous system activity in animals and man. Insulin may be a major link between changes in dietary intake and changes in central sympathetic outflow. Caloric restriction reduces, and carbohydrate administration increases blood pressure in spontaneously hypertensive rats, changes consistent with a primary effect of caloric intake on sympathetic nervous system activity. Stimulation of the sympathetic nervous system by overfeeding may contribute to the development and maintenance of hypertension in biologically-predisposed animals and man. The association of obesity and hypertension may reflect chronic overfeeding, although diet-induced changes in sympathetic nervous system activity may affect blood pressure in non-obese individuals as well.

Adolescent↗
PubMed1982

Effect of age on insulin stimulation of sympathetic nervous system activity in man.

Previous studies have shown that oral glucose increases plasma norepinephrine (NE) in man, an effect which is more pronounced in the elderly. Recently we have shown that hyperinsulinemia results in a dose-dependent increase in sympathetic nervous system (SNS) activity in young men independent of changes in blood glucose. We now report studies of the influence of hyperinsulinemia on SNS activity in healthy elderly. Euglycemic glucose clamp studies were performed at 2 insulin infusion rates, 2 mU/kg/min (young 22-37 yr, n = 7; old 63-77 yr, n = 9) and 5 mU/kg/min (young 22-36 yr, n = 7; old 64-75 yr, n = 5) nonobese men. Control studies were performed in 5 young and 3 old subjects. In control studies there were no significant changes in NE or cardiovascular measures in either group. Insulin infusion at 2 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) pulse (p less than 0.05), pulse pressure (p less than 0.005) and double product (pulse x systolic pressure) (p less than 0.01). In contrast 2 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to an increase in pulse pressure (p less than 0.01). The changes in NE at this insulin infusion dose were greater in the young than in the old (p less than 0.005). Insulin infusion at 5 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) mean arterial blood pressure (MABP) (p less than 0.001), pulse pressure (p less than 0.001) and double product (p less than 0.001). In contrast 5 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to a decrease in MABP (p less than 0.001) only. The change in NE and MABP at this insulin infusion dose were greater in the young than in the old (p less than 0.001) for each). In the young group the increases in NE were greater during the 2 mU/kg/min studies than in the control studies (p less than 0.001) and the increases in NE during the 5 mU/kg/min studies were greater than during the 2 mU/kg/min studies (p less than 0.001). In the old group there were no differences in NE or cardiovascular measures between the control, 2 mU or 5 mU insulin infusions. These studies indicate diminished insulin-induced SNS activation in the elderly. The disparity in the elderly between the enhanced SNS response to oral glucose and the blunted response to intravenous insulin and glucose suggests that splanchnic factors may mediate the SNS activation after oral glucose.

Adult↗
PubMed1982

Initiation, duration and dissipation of diet-induced changes in sympathetic nervous system activity in the rat.

Previous studies in this laboratory have demonstrated that 48 hr of fasting suppresses and 72 hr of sucrose feeding (a model of voluntary overfeeding) stimulates sympathetic nervous system activity in rats. The experiments described here were undertaken to establish whether these diet-induced change in sympathetic activity occur in the early phases of a fast and whether they persist beyond a 3 day period of overfeeding. The results indicate that changes in cardiac norepinephrine turnover can be detected during the first 24 hr of fasting or overfeeding, and that the increase in cardiac norepinephrine turnover induced by sucrose overfeeding is sustained over 8 days of sucrose administration.

Animals↗
PubMed1982

Effect of diet and cold exposure on norepinephrine turnover in brown adipose tissue of the rat.

Brown adipose tissue (BAT) is an important site of adaptive changes in thermogenesis in the rat. The sympathetic nervous system, which richly supplies BAT, is thought to play an important role in the regulation of BAT thermogenesis because catecholamines stimulate and beta adrenergic blocking agents inhibit oxygen consumption in this tissue. The present studies were carried out to assess directly sympathetic activity in BAT in response to cold exposure and to changes in dietary intake, both of which alter heat production in the rat. Sympathetic activity was determined from the rate of norepinephrine (NE) turnover in interscapular brown adipose tissue (IBAT) after preliminary experiments validated the use of NE turnover techniques in IBAT. Acute exposure to 4 degrees C increased NE turnover in IBAT 4- to 12-fold compared with ambient temperature controls, depending upon the interval over which the turnover measurement was made, while in the heart NE turnover doubled in response to the same cold stimulus. In animals exposed to cold continuously for 10 d before study, NE turnover measurements in IBAT and in the heart were elevated comparably to those obtained during acute exposure. Alterations in feeding were also associated with changes in NE turnover in IBAT. Fasting for 2 d decreased NE turnover in IBAT (-35% from 29.2+/-4.2 ng NE/h to 18.9+/-5.9) and in heart (-52%). In animals fed a "cafeteria" diet, a model of voluntary overfeeding in the rat, NE turnover was increased in both IBAT (+108% from 24.8+/-4.5 ng NE/h to 51.7+/-6.8) and heart (+66%). Because ganglionic blockade exerted a greater effect on NE turnover in IBAT in cafeteria-fed rats than in controls, the increase in NE turnover in IBAT with this overfeeding regimen reflects enhanced central sympathetic outflow. Thus NE turnover techniques can be satisfactorily applied to the assessment of sympathetic nervous system activity in IBAT. The experiments reported here demonstrate changes in sympathetic activity in IBAT that parallel known adaptive changes in heat production in the rat. These studies, therefore, support the concept that the increased thermogenesis of chronic cold exposure and of cafeteria feeding occur by similar mechanisms and imply an important role for the sympathetic nervous system, mediated in part through BAT, in the regulation of energy balance in the rat.

Adipose Tissue, Brown↗
PubMed1982

Effects of 2-deoxy-D-glucose on the cardiac sympathetic nerves and the adrenal medulla in the rat: further evidence for a dissociation of sympathetic nervous system and adrenal medullary responses.

In rats and mice, fasting suppresses and sucrose overfeeding stimulates sympathetic nervous system (SNS) activity. Fasting hypoglycemia in rats suppresses SNS activity while stimulating adrenal medullary catecholamine release. Administration of 2-deoxy-D-glucose (2-DG), an inhibitor of intracellular glucose metabolism, also stimulates the adrenal medulla. The studies reported here were undertaken to determine the SNS response to chronic 2-DG administration and to test the hypothesis that diet-induced changes in SNS activity are related to central nervous system glucose metabolism. Ingestion of 2-DG caused an increase in urinary epinephrine excretion and significant depletion of adrenal epinephrine content, both indices of adrenal medullary stimulation. Chronic sc injections of 2-DG in animals with normal or increased food consumption caused simultaneous suppression of cardiac sympathetic nerve activity, as evidenced by diminished cardiac [3H]norepinephrine turnover, and stimulation of adrenal medullary epinephrine release. Parenteral 2-DG administration to adrenalectomized rats also caused suppression of cardiac sympathetic activity. Thus, this response to neuroglycopenia is independent of adrenal medullary catecholamine release. These results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity.

Adrenal Medulla↗
PubMed1982

Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.

The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.

Adult↗
PubMed1981

Effect of ingestion of meat on plasma cholesterol of vegetarians.

In a controlled trial, 21 strict vegetarians were studied prospectively for eight weeks: a two-week control period of the usual vegetarian diet was followed by four weeks, during which 250 g of beef was added isocalorically to the daily vegetarian diet and then by two weeks of the control diet. Plasma high-density lipoprotein-cholesterol did not change during the study, whereas plasma total cholesterol rose significantly by 19% at the end of the meat-eating period. Systolic blood pressure (BP) increased significantly during the meat eating by 3% over control values, whereas diastolic BP showed no major changes. Plasma renin activity, prostaglandin A and E levels, and urinary kallikrein, norepinephrine, and epinephrine excretions were within normal limits and did not change notably throughout the trial. The study suggests an adverse effect of consumption of beef on plasma lipid and BP levels.

Adult↗
PubMed1981

Effect of oral sucrose on blood pressure in the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) increased carbohydrate intake without alteration in sodium intake is associated with elevated blood pressure. One week of feeding sucrose-supplemented chow increased blood pressure an average of 14mm Hg (9%) in three separate groups of SHR, but did not affect blood pressure in normotensive rats of the same strain (Wistar-Kyoto-WKY). Fat supplementation (isocaloric to sucrose) was without effect on blood pressure in SHR. These data are consistent with the hypothesis that diet-induced increases in sympathetic activity may elevate blood pressure in susceptible animals.

Animals↗
PubMed1981

Impact of age on basal and diet-induced changes in sympathetic nervous system activity of Fischer rats.

Studies were performed to assess the effect of age on basal sympathetic nervous system activity and on diet-induced changes in sympathetic activity. The rate of norepinephrine turnover in various tissues was measured as an index of sympathetic nervous system activity. In ad lib fed male Fischer 344 rats aged 3 to 24 months, there were no age-related differences in norepinephrine turnover in heart, liver, kidney or pancreas. Throughout the same age range, norepinephrine turnover was greater in organs of sucrose fed than in organs of fasted animals. Diet-induced changes in sympathetic activity thus persist throughout the age range studied.

Aging↗