Effects of amphetamine on catecholamine levels and turnover in discrete hypothalamic areas.
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Animals↗
Biomedical subjects
B E Levin
Publications and source records attributed to B E Levin.
Ultradian rhythms in cognitive functions and their relationship to visceral processes.
Visceral and behavioral data were repeatedly sampled over time in 7 men performing tests of eye-hand coordination and of recall. Spectrum analysis of behavioral data showed peaks in the ultradian range which for the group were significantly different from white noise. Relations between visceral and behavioral data were not striking. However, relations between (a) epinephrine and indices of sympathetic tone (i.e., norepinephrine or heart rate) and (b) ongoing performance were positive and the highest of all tested.
Activity Cycles↗
Plasma catecholamine and cardiovascular responses following hypothalamic stimulation in the awake cat.
Ninety-three hypothalamic sites were electrically stimulated, using constant parameters, in awake, restrained cats to determine those regions which maximally activated the sympatho-adrenal (SA) and cardiovascular (CV) systems. Plasma catecholamine levels were measured over time following hypothalamic stimulation; levels of norepinephrine (NE) and epinephrine (E) served as indices of adrenergic neural and adrenal medullary activities, respectively. CV parameters of heart rate (HR) and mean intra-arterial blood pressure (MAP) were continuously monitored. The greatest elevation in plasma catecholamines was elicited by stimulation of sites in the perifornical area, ventromedial nucleus, and medial forebrain bundle. Several sites were identified which preferentially elevated one of the sympatho-adrenal neurotransmitters. A differential increase in plasma E was most frequently obtained from sites around the border of the ventromedial nucleus and in the medial forebrain bundle. Differential elevation of plasma NE was observed following stimulation of sites in the anterior commissure, central preoptic area, and dorsal perifornical region posterior to the ventromedial nucleus. Sites which activated the CV and SA systems were not always coincident; those sites which activated the CV system alone tended to be located in the lateral hypothalamus.
Adrenal Medulla↗
Stress-induced heart failure.
Stress produced heart failure in cardiomyopathic hamsters (CMHs) with subclinical heart disease. CMHs exhibited a variety of peripheral manifestations of heart failure including subcutaneous edema, fluid in the abdominal and thoracic cavities, and increased organ weight. In contrast, stress did not produce heart failure in healthy hamsters. These data indicate that the presence of covert heart disease can dramatically alter the pathogenic consequences of stress.
Animals↗
Studies of origins of abnormal sympathetic function in obese Zucker rats.
To explain previously described abnormalities of sympathetic function in the genetically obese Zucker rat, the kinetics of norepinephrine (NE) metabolism were examined. Lower stress-induced levels of plasma NE in the obese rat were shown to be due to decreased release of NE because uptake of [3H]NE tracer from plasma was 45% slower in the obese compared with the lean rat. NE levels were 15, 20, and 34% lower in heart, pancreas, and interscapular brown adipose tissue (IBAT), and NE turnover rates (determined by two independent methods) were 39-48 and 43-69% lower in the pancreas and IBAT of obese compared with lean rats. In vivo synthesis of [3H]NE from [3H]dopamine by the enzyme dopamine beta-hydroxylase was 60% lower in IBAT but was equal in hearts of obese compared with lean rats. These results suggest an organ-specific decrease of NE synthesis in the obese Zucker rat, possibly due to decreased dopamine beta-hydroxylase activity in IBAT.
Adipose Tissue↗
Altered sympathetic activity during development of diet-induced obesity in rat.
Sprague-Dawley rats developed diet-induced obesity (DIO) after 3 mo on a high-fat, high-sucrose diet (DIO diet), with associated increases in total body and interscapular brown adipose tissue (IBAT) lipid content. After 7 days on the DIO diet, rats had increased levels of tyrosine hydroxylase (TH; 34%), norepinephrine (NE; 34%), and NE turnover (94%; estimated by alpha-methyl-p-tyrosine inhibition of TH) in their IBAT compared with chow-fed controls. After 3 mo on the DIO diet, NE levels and/or turnover were reduced by 27-50% in aortas, hearts, and pancreata in obese rats. While IBAT NE turnover was normal, TH inhibition failed to increase the lipid content of IBAT in obese rats as it did in controls, suggesting a postsynaptic defect in basal NE-stimulated lipolysis in this thermogenically active tissue. When obese rats were switched from the DIO diet to rat chow for 3 days, NE levels remained depressed in their hearts (25%) and aortas (14%) but were increased by 36-45% in IBAT, pancreata, and white adipose tissue. NE turnover rates and/or constants were increased by 37-110% in hearts, aortas, pancreata, and IBAT of these obese rats while there were increased IBAT TH (20%) and dopamine-beta-hydroxylase (87%) activities compared with chow-fed controls. Therefore, sympathetic activity varied markedly as a function of both dietary composition and relative body weight during the development of DIO.
Adipose Tissue↗
Relationship between sympathetic activity and diet-induced obesity in two rat strains.
Chronic diet-induced obesity developed in 50-60% of male Sprague-Dawley rats fed a relatively high-calorie diet for 90 days. The remaining rats decreased their caloric intake and resisted the development of obesity. All male Fischer F-344 rats fed this diet for 85 days became obese but to only half the degree of the obese Sprague-Dawley rats. The development of chronic obesity in both rat strains was associated with decreased norepinephrine (NE) levels in hearts and aortas and decreased NE turnover in aortas compared with chow-fed controls. However, 40-50% of the Sprague-Dawley rats did not become obese on this diet, yet showed similar findings suggesting an effect of dietary composition on sympathetic function. The more profoundly obese Sprague-Dawley rats additionally showed decreased or absent NE turnover in their hearts and pancreases. Since sympathetic function in both strains of rats with diet-induced obesity was either depressed or normal, it appears unlikely that the initial enhancement of sympathetic activity seen during short-term overfeeding plays an important continuing role in combating more chronic states of obesity in the rat.
Animals↗
Presynaptic location and axonal transport of beta 1-adrenoreceptors in the rat brain.
Interruption of the ascending noradrenergic neurons of the locus coeruleus in the rat forebrain with 6-hydroxydopamine produced a progressive accumulation, proximal to the lesion, of tritiated dihydroalprenolol binding activity over 2 days. This accumulation could be blocked by interrupting the neurons closer to their cell bodies. Competitive binding studies with the beta 2 agonist Zinterol suggested that the accumulated beta-receptors were primarily of the beta 1 subtype. These results suggest that, in the rat brain, some beta 1-adrenoreceptors are located in presynaptic, noradrenergic locus coeruleus neurons and are transported in their axons.
Adrenergic Fibers↗
Physiological effects of bed rest.
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Age Factors↗
Abnormal brown adipose composition and beta-adrenoceptor binding in obese Zucker rats.
The composition, morphology, beta-adrenergic receptor binding, and in vitro lipolysis were examined in lean and obese, 5- to 6-mo-old male Zucker rat interscapular brown adipose tissue (IBAT). IBAT pads from obese rats were heavier (283%), had more lipid (700%), and more (75%)( and larger (83%) adipocytes than those from lean rats. Also, IBAT from obese rats had no multiloculated cells, and 50% of their IBAT adipocytes were the size of white fat cells. High affinity binding for (-)-[3H]dihydroalprenolol (KD, 15-18 nM), as well as the estimated KD values for binding and the 1/2 Vmax values for adrenergic agonist-induced lipolysis were similar in isolated IBAT cells from lean and obese rats. However, adipocytes from IBAT in obese rats had 75% fewer high affinity beta-adrenergic binding sites per cell (Bmax) compared to those in lean rats. These findings are most compatible with the infiltration of IBAT by white adipocytes. Such infiltration would be expected to reduce the overall thermogenic capacity of IBAT in obese Zucker rats and thereby contribute to the maintenance of their obesity.
Adipose Tissue, Brown↗
Sympathetic activity in thyroid-treated Zucker rats.
Treatment of lean and obese 3- to 4-mo-old male Zucker rats with 0.03% thyroid powder (TP) for up to 41 days produced a decreased weight gain and carcass lipid content in obese but not lean rats, without reduction in food intake. Improved thermogenesis in TP-treated obese rats was evidenced by increased basal rectal temperatures and improved cold tolerance, although TP did not alter the lower stress-evoked levels of plasma norepinephrine (NE) or epinephrine of the obese rats. Levels of NE and/or NE turnover were lower in hearts, aortas, pancreata, interscapular brown adipose, and epididymal white adipose pads of obese compared with lean rats. Both NE levels and turnover were increased in the hearts and aortas of TP-treated obese rats, suggesting increased sympathetic activity in these organs. Basal but not stress-evoked hyperglycemia, hyperinsulinemia, and hyperglycerolemia in the obese rats were partly or totally corrected by TP treatment as was defective in vivo utilization of fatty acids. Therefore 0.03% TP administration had a selective effect on the obese Zucker rat compared with the lean and led to decreased weight gain associated with improved thermogenesis. These effects appeared to be related in part to increased sympathetic function in some organs and improved utilization of fatty acids.
Animals↗
Defective catecholamine metabolism in peripheral organs of genetically obese Zucker rats.
Catecholamine (CA) metabolism in peripheral organs of lean and obese, 3-4 and 7-8 month (mo) old male Zucker rats was studied to define further the known abnormalities of peripheral sympatho-adrenal functions in the obese rat. Norepinephrine (NE) levels in all sympathetically innervated organs from obese rats (aorta, heart, pancreas, brown adipose tissue and white adipose tissue) were decreased to 9-55% of those in lean rats at 3-4 mo. NE turnover, measured by inhibition of tyrosine hydroxylase (TH) with a-methyl-p-tyrosine, was also decreased in these same organs. NE levels and turnover were also decreased (by 50-95%) in many, but not all organs assayed of 7-8 mo old obese rats, while there were inconsistent changes in organ dopamine and epinephrine levels at both ages. Decreased NE metabolism was associated with decreased dopamine-beta-hydroxylase (D beta H) activity in every organ assayed from obese rats at 3-4 mo and 7-8 mo of age except in the superior cervical ganglia of 7-8 mo old rats. There were no consistent changes in TH or phenylethanolamine-N-methyltransferase activities. In 3-4 mo old obese rats, decreased D beta H activity was associated with decreased immunoprecipitable enzyme protein in the hearts but not in the adrenal glands, where differences in the affinity for substrate appeared to explain the activity differences. These results suggest that the previously reported defect in stress-induced plasma NE levels in obese rats could be explained by decreased D beta H activity in nerve terminals of their sympathetic nervous system and that, in this case, D beta H may play an important role in the regulation of NE synthesis.
Adipose Tissue↗
Reserpine effect on the axonal transport of dopamine-beta-hydroxylase and tyrosine hydroxylase in rat brain.
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Animals↗
Humoral indices of stress in rats.
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Animals↗
Metabolic and sympatho-adrenal abnormalities in the obese Zucker rat: effect of chronic phenoxybenzamine treatment.
The obese Zucker rat manifests a number of physiologic and metabolic abnormalities which are controlled or modulated by the sympatho-adrenal system. The interrelationship of these was examined by subjecting 3-4 month old male, homozygous lean and obese Zucker rats to various stresses which are known to activate the sympatho-adrenal system, and by chronic (16-19 days) phenoxybenzamine (PBZ) treatment to block alpha-adrenergic receptors. Both obese and lean PBZ treated rats gained only 1% and 10% of the body weight of their respective control rats during the treatment period, while only the lean rats had a significant reduction (20%) in food intake. Control obese rats failed to maintain rectal temperature after 4 hr at 7 degrees C and their relative output of plasma catecholamines (CA) to cold stress, as measured from indwelling atrial cannulae, was decreased. PBZ treatment did not alter this rectal temperature response although it was associated with increased baseline norepinephrine levels (at ambient temperature 21-22 degrees C) and relative output of CA in the obese rats, suggesting tat sympathetic neural activity was increased under these circumstances. No abnormalities of sympatho-adrenal function, as reflected in plasma CA levels, were found in treated or control obese rats immobilization for 1 hr followed by decapitation. Simultaneously obtained baseline plasma glucose levels were similar in untreated lean and obese rats, but insulin and glycerol levels in the obese rat were 1350% and 213% of lean values, respectively. During sequential stresses, the obese rats became markedly hyperglycemic and hyperglycerolemic compared to the lean rats, while insulin levels were decreased more in the obese than lean rats (12-15% versus 34-35% of controls, respectively). PBZ affected insulin levels only in the obese rats, reducing their baseline levels by 4-fold and stressed induced levels to those seen in the lean control rats. These results suggest that some of the metabolic and physiologic abnormalities of the obese Zucker rat which are modulated by the sympatho-adrenal system can be normalized by procedures which increase sympatho-adrenal activity.
Animals↗
Ultradian rhythm of plasma norepinephrine in rats.
This study examined the possibility that laboratory rats exhibit ultradian plasma catecholamine rhythms. Four rats were prepared with chronic venous cannulas. After recovery, blood was sampled every 15 min for 8 h. Spectrum analysis revealed ultradian norepinephrine rhythms with spectral peaks around 80-90 min and around 40 min. However, no reliable ultradian rhythms were found for epinephrine. Ultradian norepinephrine rhythms appeared to be synchronized across three of the four rats, suggesting that the rhythm can be synchronized by some environmental stimulus. Thus, rats exhibit ultradian norepinephrine rhythms similar to those found in humans and in rhesus monkeys, indicating (a) that laboratory rats can be used to study the biological mechanisms of ultradian rhythms and (b) that ultradian oscillations of sympathetic function are a common property of mammalian systems.
Animals↗
Effects of reserpine on fast, intermediate and slow axonal transport of proteins in rat locus coeruleus neurons.
The effects of a single injection of reserpine (5 mg/kg, i.p.) on protein turnover and axonal transport (AT) in locus coeruleus (LC) noradrenergic neurons was investigated in the rat. Reserpine pretreatment, at intervals of 1--21 days prior to [3H]-fucose or leucine injection into the LC, resulted in marked alterations in the turnover of [3H]glycoproteins and proteins in the LC and hypothalamus which were present for up to 14 days and varied according to the time after reserpine pretreatment. Reserpine produced an intermittent blockade, of variable degree, in rapidly and intermediately transported proteins for up to 2 weeks following injection. Slow AT was uniformly decreased over the first 10 post-treatment days to 2--42% of controls. Blockade and not a change in the rate or time of onset of transport appeared to be responsible for the observed changes. The suggested mechanism for these alterations is a re-ordering of metabolic priorities in the synthesis and transport of proteins in these noradrenergic cells secondary to a reserpine-induced depletion of norepinephrine in the nerve terminals.
Animals↗
Abnormal sympatho- adrenal function and plasma catecholamines in obese Zucker rats.
The functional integrity of the peripheral sympathetic nervous system and adrenal medulla was assessed in homozygous, lean and obese, 7--8 month old male Zucker rats by the changes in plasma catecholamines during cold and immobilization stresses. Five of eight obese, but no lean rats died during a 24 hr cold stress (4--7 degrees C) from hypothermia. While both lean and obese rats had decreased rectal temperatures after 4 hr of cold stress, the obese had lower temperatures, relatively less of an increase of plasma norepinephrine (NE) and epinephrine (E) than the lean rats, and were unable to consistently maintain their temperatures even during intravenous NE infusions. Obese rats had lower rectal temperatures and higher plasma NE and dopamine levels at 21--22 degrees C ambient temperature, a relative failure to increase plasma NE and E levels after 1 hr of immobilization, but normal or supranormal plasma catecholamine levels after decapitation compared to the lean rats. These results suggest that the obese Zucker rat has abnormalities of both peripheral sympatho-adrenal function and thermoregulation, which may play roles in the development and/or maintenance of many of the physiological and metabolic defects in this animal model of genetic obesity.
Adrenal Glands↗