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Biomedical subjects

L Landsberg

Publications and source records attributed to L Landsberg.

At least 109 records · Page 6Linked to original sources

Effect of concomitant fasting and cold exposure on sympathoadrenal activity in rats.

Fasting decreases and cold exposure increases sympathetic nervous system activity. The present studies examine the effect of fasting and cold together on sympathoadrenal function. At 4 degrees C animals fasted for 2 days excreted 29% less norepinephrine (NE) than fed animals, averaging 458 +/- 32ng NE/mg creatinine and 646 +/- 68, respectively (P less than 0.005), but 122% more epinephrine (E) 77.9 +/- 11.7 ng E/mg creatinine and 35.1 +/- 6.7, respectively (P less than .01). Fasting for 2 days reduced cardiac NE turnover, a direct measure of sympathetic neuronal activity, 33% in animals at 22 degrees C from 28.2 +/- 3.6 ng NE . heart-1 . h-1 to 18.9 +/- 4.8 (95% confidence intervals) and 25% in animals acutely exposed to 4 degrees C from 60.7 +/- 8.0 to 45.6 +/- 9.5. Similar reductions in urinary NE excretion and cardiac NE turnover were observed in adrenal-demedullated rats. Thus fasting at 4 degrees C lowers sympathetic activity and enhances adrenal medullary secretion. This pattern of decreased sympathetic and increased adrenal medullary activity, previously seen with fasting hypoglycemia, suggests an important role for the adrenal medulla in internal homeostasis at times when the sympathetic nervous system is suppressed.

Adrenal Medulla↗

Norepinephrine turnover in lung: effect of cold exposure and chronic hypoxia.

The lung contains sympathetic efferent nerves, but their participation in conditions associated with sympathetic nervous system activation is unknown. To assess sympathetic activity in lung during cold exposure and hypoxia, the measurement of radiolabeled norepinephrine (NE) turnover was carried out in this organ. In preliminary studies this technique, which measures in vivo the activity of sympathetic nerves in an individually innervated organ, was validated for use as a measure of sympathetic activity in rat lung. NE turnover was then measured in unanesthetized rats during cold (4 degrees C, 24 h) and hypobaric hypoxic (PB = 380 Torr, 7 days) exposure. Cold exposure increased calculated NE turnover rate in lung by 63% from 4.2 +/- 1.4 to 6.8 +/- 1.6 ng NE.organ-1.h-1 (95% confidence limits). Chronic hypobaric hypoxia increased NE turnover rate in lung by 114% from 4.0 +/- 1.8 to 8.6 +/- 2.4 NE.organ-1.h-1. Thus NE turnover techniques are applicable to rat lung and demonstrate increased sympathetic activity during cold exposure and chronic hypoxia.

Animals↗

Diet and the sympathetic nervous system: relationship to hypertension.

Studies demonstrating an importance effect of dietary intake on the activity of the sympathetic nervous system of the rat are described. Utilizing techniques to measure the turnover rate of norepinephrine in heart, fasting has been shown to suppress, while overfeeding sucrose stimulates, the sympathetic nervous system. Studies in the spontaneously hypertensive rat (SHR) demonstrate that diminished caloric intake, or fasting, with maintenance of normal sodium intake, lowers the blood pressure; conversely, overfeeding sucrose on a constant sodium intake increases blood pressure in the SHR. Overfeeding an isocaloric ration of fat, in contrast to sucrose, has no effect on blood pressure in the SHR. Blood pressure responses in the normotensive Wistar-Kyoto (WKY) strain are in the same direction but much less marked than in SHR. The sympathetic nervous system response to fasting and sucrose overfeeding in the SHR resemble those that occur in WKY and other normotensive rat strains, at least in so far as the heart is concerned. These studies, thus, raised the possibility that diet-induced changes in sympathetic nervous system activity may contribute to diet-induced changes in blood pressure. According to this hypothesis the beneficial effect of weight loss in obese hypertensive subjects, and conversely, the detrimental effect of weight gain on the development of hypertension may reflect corresponding diet-induced changes in sympathetic activity. The well known relationship between obesity and hypertension may, therefore, derive at least in part from an effect of dietary intake on the sympathetic nervous system.

Animals↗

Adrenergic modulation of extrarenal potassium disposal.

We studied the role of catecholamines in the regulation of potassium homeostasis in nine healthy subjects given intravenous potassium chloride (0.5 meq per kilogram of body weight) in the presence and absence of propranolol. Potassium infusion elevated serum potassium 0.6 +/- 0.09 meq per liter (mean +/-S.E.M.). Addition of propranolol augmented the rise (0.9 +/- 0.05 meq per liter) and prolonged the elevation in serum potassium without decreasing urinary potassium excretion. In a separate study, the same potassium load was administered with a concomitant infusion of epinephrine in five subjects. Epinephrine markedly blunted the increment in serum potassium (0.1 +/- 0.06 meq per liter) while reducing renal potassium excretion. Plasma aldosterone was not altered by the experimental procedures. Serum insulin fell minimally in the presence of propranolol but was unaffected by epinephrine. beta-Adrenergic blockade impairs and epinephrine enhances extrarenal disposal of an acute potassium load. These findings suggest that in patients with impaired potassium disposal, the risk of hyperkalemia may be increased when sympathetic blockade is induced.

Adrenergic beta-Antagonists↗

Enhanced plasma norepinephrine response to upright posture and oral glucose administration in elderly human subjects.

Plasma norepinephrine (NE) levels in response to upright posture and to oral glucose ingestion were measured in healthy young and old (greater than 65 yr of age) subjects. Peak plasma NE concentrations with standing were higher in the elderly (1334 +/- 146 pg/ml versus 855 +/- 46; p less than 0.05) and plasma NE remained elevated in the elderly compared with the young subjects even after 15 min of recumbent resting. Following oral glucose plasma NE rose higher in the elderly (79% compared with 32% in the young) and peaked later (120 min after ingestion compared with 60 min in the young). Cardiovascular changes with upright posture and with oral glucose were similar in young and old. Alterations in disappearance of NE from the circulation could not account for the greater elevations in plasma NE concentration in the elderly either, since the rates of fall in circulating NE levels following termination of an NE infusion were the same in both groups. The metabolic clearance rate of NE was unchanged. Thus, the plasma NE responses to stimulation by standing and by oral glucose ingestion are enhanced in elderly subjects.

Adolescent↗

Impaired suppression of sympathetic activity during fasting in the gold thioglucose-treated mouse.

Sympathetic activity in rats and mice is diminished by fasting and increased by sucrose feeding. The central neural mechanisms coordinating changes in the functional state of sympathetic nerves with changes in dietary intake are unknown, but a role for neurons in the ventromedial hypothalamus (VMH) is suggested by the existence of sympathetic connections within the VMH and the importance of this region in the regulation of feeding behavior. To investigate the potential role of the VMH in dietary regulation of sympathetic activity [(3)H]norepinephrine turnover was measured in the hearts of fasted and sucrose-fed mice after treatment with gold thioglucose (AuTG). In control mice, norepinephrine (NE) turnover was 1.60+/-0.92 ng NE/heart per h (95% confidence limits) after 1 d of fasting and 4.58+/-0.98 after 3 d of sucrose feeding, although, in AuTG-treated mice, cardiac NE turnover in fasting was 5.45+/-1.56 and with sucrose feeding, 5.44+/-0.76. Experiments with ganglionic blockade indicate that the absence of dietary effect on NE turnover in AuTG-treated mice reflects a corresponding lack of change in central sympathetic outflow. AuTG administration, therefore, disrupts dietary regulation of sympathetic activity by abolishing the suppression of sympathetic activity that occurs with fasting. This effect of AuTG is unrelated to duration of fasting (up to 3 d) and is specific for AuTG because neither treatment with another gold thio compound (gold thiomalate) nor the presence of genetic obesity (ob/ob) prevented fasting suppression of sympathetic activity. Moreover, AuTG treatment did not impair sympathetic activation by cold exposure (4 degrees C) nor adrenal medullary stimulation by 2-deoxy-d-glucose. Thus, AuTG treatment selectively impairs dietary regulation of sympathetic activity, possibly by destruction of neurons in the VMH.

Adrenal Glands↗

Sympathoadrenal activity in fasting pregnant rats. Dissociation of adrenal medullary and sympathetic nervous system responses.

The pattern of urinary catecholamine excretion in fasting differs in pregnant and nonpregnant rats, which suggests that the sympathoadrenal response to fasting is altered by pregnancy. In fasting nonpregnant animals, urinary norepinephrine (NE) excretion decreases and epinephrine (E) excretion remains unchanged, whereas the excretion of both catecholamines rises significantly with refeeding. In contrast, fasting third-trimester pregnant rats exhibit a 420% increase in urinary E and a 345% increase in urinary NE, elevations which fall with refeeding. Specific evaluation of sympathoadrenal activity in fasting pregnant rats reveals stimulation of the adrenal medulla and suppression of sympathetic nerves. In fasting third-trimester rats the adrenal content of E is 37% lower in innervated adrenals as compared with contralateral denervated glands, which indicates the presence of neurally-mediated adrenal medullary activation. Adrenalectomy completely abolishes the fasting-induced rise in urinary E and NE in pregnant rats. Studies with 2-deoxy-D-glucose suggest that stimulation of the adrenal medulla results from hypoglycemia, which is present after 3 d of fasting in pregnant rats (plasma glucose 36.7 mg/dl). Sympathetic nervous system activity, as measured by [(3)H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl. The calculated NE turnover rate is 44% lower in 2-d fasted pregnant rats than in fed pregnant animals (17.6 +/- 1.3 vs. 31.3 +/- 1.8 ng NE/heart per h, respectively). Thus adrenal medullary and sympathetic nervous system responses in fasting pregnant rats appear to be dissociated, which suggests that diet-induced changes in sympathetic activity and stimulation of the adrenal medulla by hypoglycemia may be independently regulated.

Adrenal Medulla↗

Excretion and metabolism of catecholamines by the isolated perfused rat kidney.

The excretion and metabolism of labeled epinephrine and norepinephrine by the isolated, perfused rat kidney were studied. The excretion of both catecholamines significantly exceeded the amount filtered, thus providing direct evidence of net tubular secretion. Renal clearance of epinephrine was significantly greater than that of norepinephrine. Tubular secretion was a linear function of the concentration of unbound catecholamine in the medium with no demonstrable tubular maximum at the concentrations studied. The isolated kidney removed catecholamines from the medium by metabolism as well as excretion in the urine. O-Methylation was the major metabolic route and O-methylated metabolites were rapidly excreted and concentrated in urine. Preferential excretion and metabolism of epinephrine were confirmed in double-label experiments in which [14C]epinephrine and [3H]norepinephrine were perfused together. The ratio of 14C:3H in urine exceeded that in perfusion medium for total radioactivity as well as for catecholamines and O-methylated amines. The present study thus provides direct evidence for (a) net tubular secretion of epinephrine and norepinephrine with a direct relationship between secretion and medium concentration; (b) significant renal metabolism of both epinephrine and norepinephrine with O-methylation as the major metabolic route; and (c) preferential excretion and metabolism of epinephrine.

Animals↗

High plasma norepinephrine concentrations at birth in infants of diabetic mothers.

Analysis of plasma norepinephrine (NE) concentrations in umbilical artery and vein from infants of diabetic and nondiabetic mothers revealed high plasma NE values in those of diabetic mothers. While birth weight and arterial plasma NE did not correlate in infants of nondiabetic mothers (r = 0.07, NS), birth weight and plasma NE were related inversely in infants of diabetic mothers (r = -0.73, P less than 0.05).

Birth Weight↗