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Effect of intravenous glucagon on urinary catecholamine excretion in normal man.

We have evaluated intravenous glucagon as pharmacologic stimulus to adrenal catecholamine secretion in normal human subjects. Urinary epinephrine and norepinephrine were measured at two hourly intervals before and after the intravenous injection of saline, 4 mg glucagon, or 0.1 mu/kg crystalline insulin. Urinary epinephrine was increased 2.3-fold over baseline after both saline and glucagon. By contrast, insulin hypoglycemia produced a 24-fold rise in urinary epinephrine. No rise in urinary norepinephrine was detected in any test. Under the conditions of this study, we conclude that epinephrine excreted after glucagon injection is due to the stress of the test itself. In normal man, glucagon either does not stimulate adrenal catecholamine secretion, or the effect is too small to measure. By contrast, in pheochromocytoma, glucagon may be specific for catecholamine secretion, based on data from the literature. In normal subjects, insulin hypoglycemia remains the only proved method for assessing adrenal catecholamine reserve.

Adrenal Glands↗

Nutrition-aging influence of catecholamine-promoted lipolysis.

Male SPF Fischer 344 rats were fed ad lib. (group A) or 60% ad lib. intake (group R) from 6 wk of age. The group R rats had a markedly increased median length of life. Starting at 6 mo of age, rats were periodically killed and free adipocytes prepared from the epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the effects of age on the promotion of lipolysis by catecholamines. At 6 mo of age, the response of the adipocytes from group A and group R rats was similar when the data are expressed as mumole glycerol released/10(6) adipocytes. With increasing age, however, this lipolytic response to catecholamines of group A rats markedly declined. The catecholamine-stimulated lipolysis/10(6) adipocytes from group R rats changed little between 6 and 18 mo of age, and the decline noted after 18 mo of age was less marked than that occurring in adipocytes from group A rats. The data based on rates of lipolysis/10(6) adipocytes indicate that it is the lifelong nutritional history of a rat population that determines the age-related changes in responsiveness of adipocytes to catecholamines. However, if the data are expressed per sq mm of adipocyte surface, a somewhat different picture emerges. These data are presented and their relevance is discussed.

Adipose Tissue↗

Role of catecholamines in regulation by feeding of energy balance following chronic exercise in rats.

Two experiments examined the contribution of the two catecholamines--epinephrine (EPI) and norepinephrine (NE)--to the control of food intake and body weight gain in male rats during chronic exercise. Urinary excretion of both catecholamines rose significantly and was positively correlated to food intake inhibition (NE, n = 54, r = 0.394, p less than 0.01; EPI, n = 54, r = 0.428, p less than 0.01). Oral ingestion of the non-selective beta-adrenoceptor blocking drug, pindolol, abolished the food intake reduction induced by exercise. Furthermore, rats that were treated with pindolol gained weight at a higher rate than untreated rats. These findings are consistent with the idea that catecholamines contribute to post-exercise inhibition of food intake and reduction of body weight in male rats. However, the exact physiological mechanism of catecholamine-induced decrease in food intake remains to be elucidated.

Animals↗

Changes of adrenal catecholamines and their synthesizing enzymes during ontogenesis and aging in rats.

Male Wistar specific-pathogen-free rats aged 2, 7, 17, 30, 60, 120, 200, 360 and 600 days, all killed in experiment on the same day, were examined. The body weight significantly increased until the 200th day, the weight of adrenals until the 120th day and the adrenal protein content until the 30th day of life. The adrenaline content of the adrenals increased continuously during the 600 days studied. Adrenal noradrenaline content increased rapidly over the first 17 days, remained at a stable level until the 120th day, and rose to a higher level after 200 days. The activity of adrenal catecholamine-synthesizing enzymes also increased with age: tyrosine hydroxylase gradually increased until the 360th day, dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase until the 200th day. Our results demonstrate that, in the rat, during development there is a gradual increase of adrenal weight, adrenaline content, tyrosine hydroxylase and phenylethanolamine-N-methyl transferase activity until maturation (120th day), whereas the adrenal noradrenaline content reaches the adult values earlier, around the 17th day. During aging, adrenal catecholamines significantly increase when compared to young-adult rats (120-day-old), probably due to the elevated activity of the adrenal catecholamine-synthesizing enzymes. The increased adrenal catecholamine levels in old animals might be connected with a higher incidence of cardiovascular diseases in aged.

Adrenal Glands↗

Catecholamines decrease leukotriene B4 and increase thromboxane B2 synthesis in A23187-stimulated human whole blood.

Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic compound without adrenergic receptor activity) decreased leukotriene (LT)B4 synthesis in A23187-stimulated human whole blood. Salbutamol, a non-catecholic beta 2-adrenergic agonist, did not influence LTB4 synthesis. Catecholamines stimulated thromboxane (TX)B2 synthesis with a concomitant inhibition of LTB4 synthesis; caffeic acid and salbutamol did not stimulate TXB2 synthesis. These results, obtained in A23187-stimulated whole blood, which also takes into account the complex interaction between different cell types, are similar to our previous results with polymorphonuclear leukocytes. Catecholamines show an opposite effect on lipoxygenase and cyclooxygenase pathways, which may give rise to a marked change in LT/TX ratio in physiological or pathological conditions where sufficient concentrations of catecholamines are present.

Calcimycin↗

Activation of GABAA receptors in hypothalamus modulates PGF2 alpha- or PGE2-induced catecholamine secretion in rats.

We previously reported that injection of PGF2 alpha into the third cerebral ventricle produces hyperglycemia and hyperthermia associated with catecholamine secretion in anesthetized rats. We have also studied the potency of catecholamine secretion induced by injecting PGE2 or PGF2 alpha into the third cerebral ventricle and the effect of the GABA-selective agonist, muscimol, on the catecholamine secretion induced by PGE2 or PGF2 alpha. Administration of 50 micrograms of PGE2 into the third cerebral ventricle increased norepinephrine secretion to a greater extent than the same dose of PGF2 alpha, whereas the latter increased epinephrine secretion to a greater degree. These effects paralleled the potencies of the hyperglycemic and hyperthermic effects of PGF2 alpha and PGE2, respectively. Simultaneous injection of 2.5 nmol of muscimol into the third cerebral ventricle with 50 micrograms of PGF2 alpha or PGE2 completely suppressed epinephrine and norepinephrine secretion induced by PGF2 alpha or PGE2. These findings suggest that central PGF2 alpha and PGE2 stimulate epinephrine and norepinephrine secretion with different potencies, and that brain GABAA receptors suppress catecholamine secretion induced by PGF2 alpha or PGE2.

Animals↗

Myocardial sensitivity to catecholamines following exposure of rats to irregular, signalled footshock.

Emotional stress is associated with an increased activity of both the pituitary-adrenal cortical system and the sympathetic-adrenal medullary systems resulting in raised plasma levels of glucocorticoids and catecholamines. There is evidence to suggest that prolonged stress induced adrenergic hyperactivity initiated myocardial pathogenesis and that this may relate to a corticosteroid catecholamine interaction. In the present study driven atrial strips removed from stressed male CSF rats were found to exhibit an enhanced sensitivity to both norepinephrine and epinephrine. These animals had previously been subjected to irregular foot shock associated with a warning signal; a situation producing a high plasma steroid level. The enhanced myocardial sensitivity to both catecholamines was observed in naive animals subjected to a single period, and persisted unchanged in animals stressed daily over a 28 day period. The hypersensitivity of the myocardium observed immediately after stress was maintained for at least 24 hr, whereas the circulating steroid level had returned to control values within 3 hr. In animals subjected to regular stress without a warning signal, a situation producing a much lower steroid level, no enhanced myocardial sensitivity was observed. While the aetiology of the phenomenon of enhanced myocardial sensitivity to catecholamines is not entirely understood, the evidence presented suggests that it may be related to the extreme elevation of circulating glucocorticoids. The sensitivity of the vas deferens however, was unaltered even though the animals were subjected to the stressor producing a high plasma steroid level. This apparent specifcity of the stress induced sensitivity change is discussed on the basis of receptor differences.

Animals↗

Plasma histamine and catecholamines during carbachol-induced bronchoconstriction in normal subjects.

To determine (1) whether changes in plasma histamine occurred during provoked bronchospasm and (2) if so, whether such changes could be related to variations in plasma catecholamines, venous plasma histamine and catecholamines were measured during a dose-response carbachol challenge in eight healthy volunteers. A significant rise in plasma histamine was observed, whereas induced bronchoconstriction was small, 80% +/- 4% of initial specific airway conductance. There was no further increase in plasma histamine, whereas induced bronchoconstriction became more marked (70%, 60%, and 50% of specific airway conductance initial value). Plasma catecholamines did not change throughout the study. We conclude that mast cell degranulation occurs during a carbachol challenge, and that the variations in plasma histamine are not related to changes in plasma catecholamines.

Adult↗

Oxytocin inhibits ACTH and peripheral catecholamine secretion in the urethane-anesthetized rat.

Oxytocin (OT) generally has a stimulatory effect on ACTH secretion both in vitro and in vivo. As part of a study of ACTH-releasing factors in hypophysial portal blood, the effects of i.v. OT administration on plasma ACTH levels were tested in urethane-anesthetized rats. Surprisingly, i.v. injection of 10 micrograms OT lowered plasma ACTH levels by about 35% (P less than 0.01). It was reasoned that this paradoxical inhibition of ACTH secretion by OT might be mediated by inhibition of the unusually high rate of peripheral catecholamine secretion in this model. Measurement of plasma catecholamines before and after i.v. administration of 10 micrograms OT revealed a 53% inhibition of EPI (P less than 0.01) and 43% inhibition of NE (P less than 0.05). Administration of the beta-adrenergic antagonist propranolol (400 micrograms) 15 min before the beginning of the experiment completely blocked the inhibitory effects of OT on ACTH secretion and in fact unmasked the stimulatory effects of OT normally seen in conscious animals and in vitro. Superfused bisected adrenal glands exposed to 10(-6) M OT for 10 min secreted more than 30% less EPI and NE than control adrenals suggesting that the inhibition of EPI and NE secretion by OT in vivo occurs, at least in part, directly at the level of the adrenal. The data support the hypothesis that peripheral catecholamines may at times be directly involved in the control of ACTH secretion and also suggest that OT, which has recently been identified in the adrenal medulla, may have important paracrine functions in the regulation of adrenal catecholamine secretion.

Adrenocorticotropic Hormone↗

Biochemical studies on the release of catecholamines from the rat carotid body in vitro.

The effects of hypoxia and carbachol on the release of newly synthesized catecholamines from superfused rat carotid bodies have been examined. Hypoxic superfusion medium was found to evoke catecholamine release which was dependent on the extracellular calcium concentration and was reduced by nitrendipine and atropine. Superfusion with the muscarinic agonist, carbachol, stimulated catecholamine release independently of the oxygen tension of the medium. The effect of carbachol on catecholamine release was abolished by atropine, suggesting that it was mediated by activation of cholinergic receptors of the muscarinic type. Both hypoxia and carbachol stimulated the release of 45Ca from carotid bodies prelabelled with 45Ca. The release of 45Ca with either stimulus was reduced by atropine and nitrendipine. These results suggest that although extracellular calcium plays an important role in the exocytotic secretory process of the carotid body, the mobilization of intracellular calcium pools may also contribute to the secretory response.

Animals↗

Cardiac function and plasma catecholamines during upright exercise in healthy young subjects.

Radionuclide left ventricular ejection fraction, left ventricular volume changes and plasma catecholamines were recorded in six healthy untrained male subjects at rest and during upright exercise at increasing work loads. During mild submaximal exercise mean left ventricular ejection fraction increased 10% because of end-diastolic dilation, while a further 4% increase of left ventricular ejection fraction was recorded at heavy submaximal exercise mainly due to increased end-systolic contraction. Great individual changes were recorded during maximal exercise. Alterations in plasma catecholamines were most pronounced at the high exercise levels indicating that changes in cardiac contractility are not linearly correlated with changes in sympathetic nervous activity. Repeat studies showed only minor variations of mean left ventricular ejection fraction and plasma catecholamines indicating an acceptable reproducibility of the measurements. Variations of both left ventricular ejection fraction and catecholamines were smaller during exercise than at rest.

Adult↗

Variation in lifestyle characteristics and catecholamine excretion rates among young Western Samoan men.

Comparisons of 13 lifestyle characteristics and the rates of urinary catecholamine excretion during typical morning activity are examined among four groups of young Samoan men in Western Samoa. The groups include 28 manual laborers, 33 sedentary workers, and 31 college students from the urban area of Apia, and 31 rural agriculturalists. Associations between the lifestyle variables and catecholamine excretion rates are also investigated in the total sample (N = 123) using correlations and multiple stepwise regression techniques. Results of the lifestyle characteristic comparisons show that the villagers have greater life satisfaction, emotional stability, agreement with Samoan customs, and familial responsibility (P less than 0.05). The catecholamine comparisons show that the villagers have lower rates of epinephrine and norepinephrine excretion than any of the Apia groups (P less than 0.05 and P less than 0.005 respectively). The regressions indicate that diet, activity, day of specimen collection and the overall lifestyle and ecological differences between the village and Apia are associated with 25 and 31% of the variation in the rates of epinephrine and norepinephrine excretion respectively. These results suggest that both psychological and habitual behavioral differences contribute to the catecholamine variation of the men in this study, and that these differences are related to the degree of participation in Western lifestyles.

Adult↗

Adrenal secretion of catecholamines evoked by chemical stimulation of trigeminal nucleus caudalis in the cat.

Microinjections of the neuroexcitatory substance L-glutamate, were made directly into various laminae of trigeminal nucleus caudalis to examine the influence of medullary dorsal horn neurons on the adrenal secretion of catecholamines in the anesthetized cat. Microinjections into the marginal layers (lamina I-II) or into the deep magnocellular portion (lamina V-VI) of nucleus caudalis ipsilateral to the adrenal vein sample evoked a prompt increase in the secretion of epinephrine and a smaller, yet consistent, increase in the secretion of norepinephrine. Injections into the magnocellular layers (lamina III-IV) had no significant effect on secretion of catecholamines. Injections into nucleus caudalis, contralateral to the adrenal vein sample, had no consistent effect on secretion suggesting that the central pathway from nucleus caudalis to the spinal cord for control of adrenal secretion of catecholamines is mainly ipsilateral. Changes in the adrenal secretion of epinephrine were not correlated with changes in adrenal venous blood flow, in arterial pressure or in heart rate. Arterial pressure was transiently increased by L-glutamate injections into the marginal layers, whereas injections into other laminae had no consistent effect. Heart rate increased regardless of the laminar site injection. The results indicate that local excitation of nucleus caudalis, in laminae that contain the majority of nociceptive neurons, evokes a consistent increase in the adrenal secretion of catecholamines, whereas excitation of neurons in laminae that mainly process non-noxious sensory input has no significant effect. It is concluded that secondary trigeminal neurons that contribute to the autonomic responses to noxious trigeminal stimuli have a similar distribution within nucleus caudalis as those that underlie the sensory-discriminative aspects of nociceptive.

Adrenal Glands↗

Distribution of catecholamines in the central nervous system of the pig.

The objective of this study was to document, through comprehensive means, normal distribution and concentration of catecholamines in various regions of the CNS of pigs, an increasingly popular animal model used for transgenic manipulation of neural genes. The effects of gonadal steroidal status on this distribution were also assessed by comparing CNS catecholamine concentrations among mature male pigs (boars), immature (gilts) and mature female pigs (sows), and adult male pigs castrated prepuberally (barrows). Dissected tissue samples from the CNS were extracted in 2 N acetic acid, filtered through a 0.2 micron filter, then quantitated by reverse-phase high performance liquid chromatography using a C-18 reverse phase column with electrochemical detection. In both boars and sows the highest concentrations of norepinephrine (NE) were found in the diencephalic areas and brain stem. Gilts exhibited elevated concentrations of NE in the olfactory bulbs (OB), hypothalamus, pons, and corpus trapezoideum-locus ceruleus (LC) compared to lower concentrations in corresponding areas of sows. Prepuberal castration of the male was associated with significantly lower NE concentrations in the striatum, periaqueductal area (PAG), pons, LC, and spinal cord. The sow exhibited significantly lower NE concentrations in the mammillary area (Mam), PAG, pons, and spinal cord than those in corresponding areas of the boar. Dopamine concentrations appeared to be similar in all areas of the brain and spinal cord studied in the sow and boar. Results demonstrated that prepuberal castration of the male appears to significantly alter the DA content of the Mam and dorsal spinal cord, in contrast to gilts who possess significantly higher concentrations of DA. It is concluded from our studies that in general, catecholamine concentrations in various regions of the brain and spinal cord of sexually mature pigs parallel distributions of neuropeptides, substance P, and methionine enkephalin, as previously reported. In addition, significant association was found between gonadal activity and catecholamine concentrations in discrete areas of the pig brain.

Animals↗

Lactate in cord blood and its relationship to pH and catecholamines in spontaneous vaginal deliveries.

The interrelationships between lactate and pH, nonadrenaline (NA), adrenaline (A) and dopamine (DA) were investigated in cord artery (CA) and vein (GV) blood at delivery. Sixty consecutive, spontaneous, vaginal deliveries with fetuses in cephalic presentation were assessed. Median gestational age at delivery was 40 weeks (range, 35-43). There were significant correlations between lactate and pH (P < 0.01), NA (P < 0.01), A (P < 0.05) and arterio-venous NA (P < 0.05) and DA differences (P < 0.01) in CA blood, while no variable correlated significantly to lactate in CV blood. The higher levels both of lactate and of catecholamines in CA blood are probably fetally derived. Dividing the material into high and low lactate subgroups (cut-off level, 75th percentile) showed a high lactate level to be associated with lower pH and higher catecholamine levels in CA blood, though the relationship was only statistically significant for pH. The levels both of catecholamines and of lactate were lower than those reported for cases of fetal distress, and reflect the lower level of fetal stress in the present series of normal deliveries. The low level of fetal stress and the differences in turnover rates between catecholamines and lactate might obscure their causal relationships, vis-a-vis fetal adaptation to extrauterine life during the course of parturition.

Delivery, Obstetric↗

Evaluation of a simple plasma catecholamine extraction procedure prior to high-performance liquid chromatography and electrochemical detection.

The modified extraction method for catecholamines described in this study is reproducible, simple, rapid, economical and relatively hazard-free. This method is based on the principle that plasma catecholamines are selectively adsorbed on acid-washed alumina at pH 8.6 and then eluted at a pH between 1.0 and 2.0. No statistically significant differences were obtained by using either 0.5 or 1.0 ml of plasma with 0.5 or 1.0 ml of Tris buffer. A 15-min mixing time during the adsorption and desorption steps was found to be practical, but any standardized time up to 1 h can be used. If the washing step was omitted, the catecholamines could not be eluted from the acid-washed alumina. To prevent dilution, the alumina had to be centrifuged and not aspirated to dryness after the washing step. An amount of 50 mg of WA-4 alumina was found to be the most practical in this study. Extracted or unextracted plasma as well as catecholamine standards were stable for four months at -20 degrees C.

Adsorption↗

Cardiovascular changes and catecholamine release following anaesthesia in Chinook salmon (Oncorhynchus tshawytscha) and snapper (Pagrus auratus).

We investigated recovery from anaesthesia in Chinook salmon (Oncorhynchus tshawytscha) with and without surgery. Fish either underwent light sedation on exposure to 60 ppm AQUI-S or surgical depth anaesthesia with 120 ppm AQUI-S. Surgical depth anaesthesia experiments were replicated using New Zealand snapper (Pagrus auratus). During light sedation, there was no evidence of catecholamine release in salmon despite changes in heart rate and blood pressure. Following surgical anaesthesia both salmon and snapper released high concentrations of catecholamines into the circulation. Plasma half-life of adrenaline in salmon was 9.3+/-0.7 min (n = 7) and in snapper was 4.4+/-3.3 min (n = 7). There was no further release of catecholamines, despite attempts by both species to escape their enclosures. Though clearance of the catecholamines was rapid, the cardiovascular effects of anaesthesia were prolonged. Dorsal aortic blood pressure (P(DA)) and heart rate (HR) were high following anaesthesia, falling by 60 min in the 60 ppm exposed salmon but remaining high in the 120 ppm group. Following anaesthesia ventral aorta blood pressure (P(VA)) in snapper was positively correlated with HR, as was P(DA) and haematocrit in salmon. Recovery of cardiovascular control processes is prolonged in recovery from anaesthesia if the fish become hypoxic.

Anesthesia↗

Influence of catecholamines on cytokine production and expression of adhesion molecules of human neutrophils in vitro.

The impact of catecholamines on cytokine production and expression of adhesion molecules by human neutrophils was evaluated in vitro. Neutrophils were separated from venous blood of healthy subjects. The generation of intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ was determined after incubation with catecholamines. Resting and lipopolysaccharide (LPS)-activated neutrophils were tested for synthesis of interleukins (IL-6, IL-8) and tumor necrosis factor alpha (TNF-alpha). In addition, the expression of the adhesion molecules CD15, CD44, and CD54 was evaluated in resting and activated neutrophils. Increasing concentrations (1 nM-1 mM) of epinephrine (EPI) were used to study the influence of activation of beta2-adrenergic receptors (beta2R) on cytokine production and adhesion molecule expression. Incubation with catecholamines induced an increase in cAMP but not Ca2+ in neutrophils. Only IL-8 was detected following stimulation with LPS and was unchanged upon co-incubation with EPI. The expression of CD15 and CD44 decreased spontaneously in vitro. The density of CD44 increased in the presence of very high doses of EPI (1 mM). Expression of CD54 on resting neutrophils increased upon activation. The density of CD54 on activated neutrophils was reduced upon co-incubation with 1 mM EPI for 6 h. However, 1 mM EPI for 12 and 18 h decreased the spontaneous loss of CD54 on resting neutrophils. Beta2R are functionally coupled to signalling cascades in human neutrophils. Nevertheless, the impact of catecholamines on IL-8 synthesis and expression of CD15, CD44, and CD54 is limited.

Antigens, CD↗