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Urinary excretion of catecholamines in hospitalized and non-hospitalized healthy children and adolescents.

Non-conjugated catecholamines were measured in morning urine samples from 111 healthy, non-hospitalized subjects aged 8-18 y and in 16 hospitalized, healthy subjects aged 12 16 y. The catecholamines were extracted by cation exchange columns and alumina adsorption and quantitated with HPLC with electrochemical detection. The concentration of catecholamines was related both to the urinary creatinine concentration and to the collecting period and body surface area. Linear regression analysis was used to estimate continuous age-related reference centiles based upon the measurements from the 111 non-hospitalized subjects. The upper limits for the adrenaline/creatinine and noradrenaline/creatinine ratios were lower than in previous studies. The excretion of adrenaline and noradrenaline per hour and m2 body surface area was higher in the 16 hospitalized than in the 74 age-matched non-hospitalized subjects. The excretion of the catecholamines expressed per hour and m2 body surface area and expressed relative to creatinine excretion, decreased with increasing age, and the excretion of adrenaline and noradrenaline per hour and m2 body surface area was higher in boys than in girls. In conclusion, standardization of urine sampling leads to more narrow ranges for urinary adrenaline and noradrenaline excretion in healthy children and adolescents.

Adolescent↗

Disappearance of catecholamine fluorescence from the adrenergic nerves in arterial grafts in rats: an experimental fluorescence histochemical study.

The disappearance of catecholamine fluorescence from the noradrenaline-containing sympathetic nerve fibres after arterial transplantation was studied using a femoral artery graft sutured to rat carotid artery. Glyoxylic acid-induced fluorescence was used to demonstrate adrenergic nerves histochemically. At six hours the network of fibres had started to degenerate, and catecholamine fluorescence from the adrenergic nerves had almost completely disappeared within 24 hours of grafting. Control specimens from normal femoral arteries showed a dense network of fluorescent adrenergic nerves. Based on observations of the relatively rapid liberation of catecholamines from the degenerating adrenergic nerves, we suggest that catecholamines liberated from degenerating adrenergic nerves may have an important role in early vasospasm in microvascular and coronary bypass surgery.

Adrenergic Fibers↗

The platelet phenolsulfotransferase is not indispensable for the sulfoconjugation of plasma catecholamines.

To investigate the role of platelets, a proposed primary site of catecholamine sulfoconjugation, we determined plasma free and sulfoconjugated catecholamines and platelet phenolsulfotransferase activity in severe platelet defficiency states. We found that even in the presence of very low platelet counts, the plasma concentrations of sulfoconjugated catecholamines were within normal limits. Although the platelet phenolsulfotransferase activity expressed per number of platelets was normal there was a considerable decrease of the total platelet phenolsulfotransferase activity. This suggests that the platelet phenolsulfotransferase is not indispensable for the sulfoconjugation of catecholamines and this process can occur elsewhere. A preliminary finding of lower platelet phenolsulfotransferase activity in platelet deficiency states with reduced platelet generation (because of reduced megakaryocytes) than in those states with a decreased platelet survival, suggests that the phenolsulfotransferase is synthesised in the megakaryocytes and the platelets are only carriers of this enzyme.

Arylsulfotransferase↗

Lasting biological effects of early environmental influences. 8. Effects of neonatal infection, perinatal malnutrition, and crowding on catecholamine metabolism of brain.

The effects of neonatal infection, perinatal malnutrition, and crowding on the metabolism of brain catecholamine were studied in specific pathogen-free mice. Metabolic turnover of catecholamine was determined by measuring the incorporation of precursor tyrosine-(14)C into brain tissue, catabolic activity of norepinephrine-(3)H at various times after intracisternal injection, and tissue levels of dopamine and norepinephrine. The rate of tyrosine incorporation was decreased by neonatal infection but was increased by perinatal malnutrition and crowding. There was no difference in catabolic activity of norepinephrine between infected, crowded, and control groups. In the malnourished group, however, the total radioactivity from norepinephrine was significantly higher than in the control group (1/2) and 2 hr after injection. The brain contents of dopamine and norepinephrine were depressed in the malnourished group. There was no significant difference in catecholamine levels between infected, crowded, and control groups. In the malnourished group, treatment of the mothers with growth hormone prevented almost completely weight loss during lactation, and also resulted in higher fetal weight. Hormone treatment restored to normal the levels of brain catecholamine and the enzymatic activity of brain tyrosine hydroxylase in progeny of malnourished mothers.

Animals↗

Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology.

The chromogranin/secretogranin proteins are costored and coreleased with catecholamines from secretory vesicles in chromaffin cells and noradrenergic neurons. Chromogranin A (CHGA) regulates catecholamine storage and release through intracellular (vesiculogenic) and extracellular (catecholamine release-inhibitory) mechanisms. CHGA is a candidate gene for autonomic dysfunction syndromes, including intermediate phenotypes that contribute to human hypertension. Here, we show a surprising pattern of CHGA variants that alter the expression and function of this gene, both in vivo and in vitro. Functional variants include both common alleles that quantitatively alter gene expression and rare alleles that qualitatively change the encoded product to alter the signaling potency of CHGA-derived catecholamine release-inhibitory catestatin peptides.

Amino Acid Sequence↗

Redox aspects of signaling by catecholamines and their metabolites.

This review covers certain novel aspects of catecholamine signaling in neurons that involve redox systems and synaptic plasticity. The redox hypothesis suggests that one important factor in neurocomputation is the formation of new synapses and the removal of old ones (synaptic plasticity), which is modulated in part by the redox balance at the synapse between reactive oxygen species (ROS) (such as hydrogen peroxide and the nitric oxide radical) and neuroprotective antioxidants (such as ascorbate, glutathione, and catecholamines). Catecholamines, in particular dopamine, which signals positive reinforcement, may play a key role in this activity. Dopamine has powerful antioxidant properties by several separate mechanisms-direct ROS scavenging, activation of the synthesis of antioxidant proteins, and possibly via dismuting complexes with iron inside endosomes or in catecholaminergic synaptic vesicles. This may contribute to synaptic growth and reinforcement-directed learning. On the other hand, catecholamines are easily oxidized to toxic quinones on the neuromelanin pathway. This might contribute under certain circumstances to synaptic deletion. Evidence is presented that abnormalities in this system may contribute to the pathogenesis of Parkinson's disease and schizophrenia.

Animals↗

Differences in left ventricular structural and functional changes between pheochromocytoma and essential hypertension. Role of elevated circulating catecholamines.

Experimental findings suggest that catecholamines increase protein synthesis and play a role in cardiac hypertrophy. We hypothesize that elevated circulating plasma catecholamines in pheochromocytoma influence cardiac structural and functional remodeling. We compared 15 patients with surgically proven pheochromocytoma and 15 with untreated essential hypertension; we matched the patients for age, sex, body surface area, and blood pressure (BP) levels. Left ventricular hypertrophy (LVH) was identified by M-mode echocardiography in six patients with pheochromocytoma and in four with essential hypertension. Among both groups there were no differences in cardiac structure, no correlation between left ventricular mass and BP, no significant differences in mitral E-F slope, no correlation between either plasma norepinephrine or plasma epinephrine levels, and no differences in the left ventricular structural indices measured. In the pheochromocytoma group, left ventricular end systolic stress and end systolic diameter were significantly lower and left ventricular percent fractional shortening was higher. Plasma norepinephrine levels were higher in the pheochromocytoma group, but did not differ among patients of that group with and without LVH. We conclude that in both pheochromocytoma and essential hypertension, only a subset of patients develop evidence of LVH, and that in pheochromocytoma, the elevation of circulating plasma catecholamines is not necessarily associated with LVH. These results indicate that factors other than catecholamines and BP determine the development of LVH in pheochromocytoma.

Adolescent↗

The adrenergic response to surgery involving cardiopulmonary bypass, as measured by plasma and urinary catecholamine concentrations.

Plasma and urinary catecholamine concentrations have been measured in 13 patients undergoing cardiac surgery involving cardiopulmonary bypass. The large and progressive increase in plasma catecholamines during bypass reported in previous studies has not been confirmed, and this may be a result of improvements in surgical, anaesthetic and perfusion techniques. The interpretation of urinary findings was complicated by the finding of a positive correlation between catecholamine excretion and urine flow-rate. The findings suggest the need to modify current concepts of the adrenergic response to cardiac surgery and bypass, and question the validity of measuring the urinary catecholamine concentration as an index of stress in these circumstances.

Adult↗

Olfactory sensitivity to catecholamines and their metabolites in the goldfish.

The current study assessed the olfactory sensitivity of the goldfish (Carassius auratus L.) to the catecholamines, their immediate precursors and metabolites by use of the electro-olfactogram (EOG). The olfactory system of the goldfish was found to be sensitive to both adrenaline and dopamine with thresholds of detection of 10(-7.8) and 10(-7.9) M respectively, but less so to noradrenaline (threshold of detection 10(-6.3) M). The 3-O-methoxy metabolites (metadrenaline, normetadrenaline and 3-O-methoxytyramine) evoked larger amplitude EOGs than the non-metabolized form with lower thresholds of detection. However, the olfactory system was less sensitive to the amino acid precursors L-tyrosine and L-DOPA, and markedly less so to the alpha-deaminated metabolites (3,4-dihydroxyphenyl glycol, 3,4-dihydroxy mandelic acid and dihydroxyphenyacetic acid). Sensitivity to metabolites, both alpha-deaminated and 3-O-methoxylated, was similar to the alpha-deaminated forms. Cross-adaptation studies suggested that, while there is some degree of commonality of the receptor mechanisms with L-tyrosine and L-serine, a proportion of the response to the catecholamines is due to distinct receptor subtypes. Similarly, the 3-O-methoxy metabolites also had (a) separate receptor mechanism(s), although, again, there was overlap with the adrenaline/dopamine receptor site(s). Presence of the alpha-adrenoreceptor antagonist prazosin or the peripheral DA(2) dopamine receptor antagonist domperidone caused partial attenuation of the EOG responses to adrenaline and dopamine, but had much less effect on the responses to their 3-O-methoxy metabolites. The beta-adrenoreceptor antagonist sotalol had no such effect. This suggests that the olfactory catecholamine receptors are structurally and functionally distinct from systemic adreno- and dopamine receptors. The current study raises the possibility that release of catecholamines or their 3-O-methoxy metabolites to the water may play a role in chemical communication.

Action Potentials↗

The catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.

We report the genetic, phenotypic, and biochemical analyses of Catecholamines up (Catsup), a gene that encodes a negative regulator of tyrosine hydroxylase (TH) activity. Mutations within this locus are semidominant lethals of variable penetrance that result in three broad, overlapping effective lethal phases (ELPs), indicating that the Catsup gene product is essential throughout development. Mutants from each ELP exhibit either cuticle defects or catecholamine-related abnormalities, such as melanotic salivary glands or pseudotumors. Additionally, Catsup mutants have significantly elevated TH activity that may arise from a post-translational modification of the enzyme. The hyperactivation of TH in Catsup mutants results in abnormally high levels of catecholamines, which can account for the lethality, visible phenotypes, and female sterility observed in these mutants. We propose that Catsup is a component of a novel system that downregulates TH activity, making Catsup the fourth locus found within the Dopa decarboxylase (Ddc) gene cluster that functions in catecholamine metabolism.

Animals↗

Acute down-regulation of antibody production following spinal cord injury: role of systemic catecholamines.

We investigated whether antibody production to antigens arising in the subarachnoid space is depressed acutely after spinal cord injury (SCI), and whether such depression is due to abnormal catecholamine levels. To assess antibody responses, ovalbumin (OVA) was injected into the spinal subarachnoid space (i.t.) of rats via an indwelling catheter after SCI at T4 or laminectomy (LAM). Antibody responses tested at days 0, 7, and 14 (d0, d7, d14) postinjury revealed that SCI animals exhibited an antibody response significantly lower than LAM animals on d7, but one that reached control levels by d14. ELISPOT assays indicated that the cervical lymph nodes, known to be innervated by superior cervical ganglia (SCG), processed i.t. OVA. The reduction in antibody production after SCI could not be mimicked with surgical deafferentation of the SCG. However, blockade of beta-adrenergic receptors prior to SCI did reverse the decrease, suggesting an adverse effect of the surge of catecholamines that accompanies the injury. Surgical removal of sympathetic inputs to the cervical lymph nodes prior to SCI failed to reverse the effect on antibody production, suggesting a systemic source of catecholamines. We conclude that antibody responses against i.t. antigens are attenuated acutely after SCI due to the massive release of systemic catecholamines that accompanies SCI.

Adrenergic beta-Antagonists↗

Testis of prepubertal rhesus monkeys receives a dual catecholaminergic input provided by the extrinsic innervation and an intragonadal source of catecholamines.

The mammalian testis is innervated by extrinsic catecholaminergic nerves and responds to catecholamines with steroid secretion. Although the primate testis has also been shown to be innervated, potential differences in the density of this innervation between immature and sexually developed individuals have not been described. A recent study demonstrated that the primate ovary contains a network of neuron-like cells and that some of these cells are catecholaminergic. It is thus possible that the male gonad is also endowed with a similar intragonadal source of catecholamines. The present study addresses these two issues. Catecholaminergic nerves were identified as such by their content of immunoreactive tyrosine hydroxylase (TH; the rate-limiting step in catecholamine biosynthesis), and in some cases by glyoxylic acid histochemistry. Fibers containing TH were abundant in testes from juvenile animals (1-2 yr of postnatal life), but the density of this innervation was not maintained in adult animals, whose testis showed only a few TH-positive fibers scattered in the interstitial tissue. Testicular norepinephrine (NE) concentration was much lower in adult than in juvenile animals, suggesting that the marked increase in testicular weight that occurs with the attainment of sexual maturity is not accompanied by corresponding changes in NE content. At the ultrastructural level, testicular nerve fibers contained pleiomorphic, dense-core and clear vesicles, suggesting the presence of catecholamines and other neurotransmitters. In addition to this extrinsic catecholaminergic innervation, prepubertal testes, but not adult gonads, contained an intrinsic population of TH-immunopositive neuron-like elements, identified as cells by confocal scanning laser microscopy. To determine whether the prepubertal monkey testis indeed expresses the TH gene, testicular RNA was subjected to reverse transcriptase polymerase chain reaction to amplify the 5' end of TH mRNA, which encodes the regulatory domain of the enzyme. The cDNA that was obtained predicts an amino acid sequence similar, but not identical, to that encoded by the alternatively spliced type 1 TH mRNA form present in the adrenal gland. These results indicate 1) that the primate testis receives a dual catecholaminergic input, one provided by the extrinsic innervation and the other by neuron-like cells located within the gonad itself, and 2) that the influence exerted by both sources on testicular function may be more prominent during the prepubertal period than in adulthood. The presence in the testis of a TH mRNA variant encoding amino acid substitutions in its 5' end suggests that regulation of testicular TH enzyme activity may include a gonad-specific component.

Aging↗

Catecholamine-secreting paraganglioma of glomus jugulare region.

A 43-year-old woman had clinical and biochemical evidence of a secreting paraganglioma of the glomus jugulare region. Catecholamine secretion was exacerbated during embolization of the tumor before surgery and resulted in a life-threatening vasomotor attack. Preoperatively, pharmacologic blockade of excessive catecholamine secretion with prazocin controlled her blood pressure, tachycardia, and symptoms. The tumor was resected and its catecholamine content measured. This case is reported to stress the importance of adequate preoperative assessment of patients with paragangliomas of the head and neck. The extreme rarity of catecholamine-secreting tumors of this region should not lead us to underestimate the morbidity and mortality of such patients undergoing surgery or any other invasive procedure whether the diagnosis is confirmed or only suspected.

Adult↗

Effects of rapid increases of desflurane and sevoflurane to concentrations of 1.5 MAC on systemic vascular resistance and catecholamine response during cardiopulmonary bypass.

BACKGROUND: Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane. METHODS: Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 degrees C) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min. RESULTS: The time-course of deltaSVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time. CONCLUSIONS: The authors' results indicate that desflurane is associated with a different hemodynamic and catecholamine response compared with sevoflurane when administered into the oxygenator's gas supply line during CPB.

Aged↗

NTS catecholamine cell recruitment by hemorrhage and hypoxia.

Immunolabelling for Fos and tyrosine hydroxylase was used to determine the patterns of activation of nucleus tractus solitarius catecholamine cells in response to graded levels of hemorrhage (0, 4, 8, 12 and 16 ml/kg) and systemic hypoxia (21, 14, 12, 10 and 8% O2) in conscious rats. Both stimuli elicited graded catecholamine cell recruitment with thresholds of 8 ml/kg and 12% O2. The majority of responsive neurons were A2 noradrenergic rather than C2 adrenergic cells. After hemorrhage most Fos-positive catecholamine cells were found below obex whereas most hypoxia-responsive cells were rostral to obex. These distinctive patterns of catecholamine cell recruitment may explain the differences in neuroendocrine responses to these stimuli.

Animals↗

Urinary catecholamine excretion and severity of PTSD symptoms in Vietnam combat veterans.

In the present study, we replicated and extended our previous findings of increased 24-hour urinary catecholamine excretion in posttraumatic stress disorder (PTSD). Dopamine, norepinephrine, and epinephrine concentrations were measured in 22 male patients with PTSD (14 inpatients and eight outpatients) and in 16 nonpsychiatric normal males. The PTSD inpatients showed significantly higher excretion of all three catecholamines compared with both outpatients with PTSD and normal controls. Dopamine and norepinephrine, but not epinephrine, levels were significantly correlated with severity of PTSD symptoms in the PTSD group as a whole. In particular, these catecholamines seemed related to intrusive symptoms. None of the catecholamines were correlated with severity of depression. The findings support the hypothesis of an enhanced sympathetic nervous system activation in PTSD, and suggest that increased sympathetic arousal may be closely linked to severity of certain PTSD symptom clusters.

Ambulatory Care↗

Hemodynamic changes, plasma catecholamine responses, and echocardiographically detected contractile reserve during two different dobutamine-infusion protocols.

We studied hemodynamic changes, catecholamine responses, and the occurrence of improved wall thickening by echocardiography during two different dobutamine-infusion protocols. Forty-three patients were studied by using a stepwise incremental dobutamine dose-infusion protocol (10-40 microg/kg/min, 3-min intervals); a subgroup of 11 patients also underwent a continuous dobutamine-infusion protocol (10 microg/kg/min for 12 min) in random order. No patient used beta-blockers. At 3-min intervals, blood pressure, heart rate, and plasma concentrations of dobutamine, epinephrine, and norepinephrine were measured. The echocardiographic improvement of wall thickening was analyzed only in paired protocols by visual assessment in left ventricular regions with normal wall motion at rest. The mean heart rate increased in the continuous and stepwise protocols from 73 to 99 and 74 to 132 beats/min. There was no significant change in blood pressure response between the two protocols. The mean plasma dobutamine concentrations during the continuous and stepwise protocols at 0, 3, 6, 9, and 12 min were 0/0; 31/38; 80/203; 106/448; and 120/692 ng/ml, respectively. In each patient, a response curve was constructed for the plasma dobutamine concentration versus heart rate. The heart rate increment and dobutamine concentration at which wall thickening was detected were similar with both protocols (14 +/- 5 vs. 12 +/- 7 beats/min) and (80 +/- 40 vs. 92 +/- 48 ng/ml; mean +/- SD). Wall thickening was noted in two of 11 patients between 0 and 3 min and 11 of 11 patients between 3 and 6 min in both protocols. Catecholamine responses during the continuous and stepwise protocols were epinephrine, 23 versus 28/28 versus 36, and norepinephrine 301 versus 323/347 versus 519. Only norepinephrine plasma concentrations increased significantly during the stepwise protocol. A 6-min dobutamine infusion was sufficient during both protocols to reach an adequate plasma dobutamine concentration, which induced a detectable increase of wall thickening in all patients. There is a significant differences between the two protocols with regard to the plasma catecholamine changes, so some of the hemodynamic effects during the stepwise dobutamine-infusion protocol may be mediated through release of endogenous catecholamines.

Adrenergic beta-Agonists↗

Long-term regulation of catecholamine formation by ouabain in cultured bovine adrenal chromaffin cells.

The long-term effects of ouabain, an inhibitor of Na+/K+ -ATPase, on catecholamine formation in cultured bovine adrenal chromaffin cells were examined. The increase in [14C]catecholamine formation from [14C]tyrosine induced by ouabain was dependent on incubation time, and its maximal effect was observed after incubation for 8 h. The stimulatory effect of ouabain was concentration dependent (10-300 nM), causing maximal stimulation at 300 nM. The formation of [14C]catecholamines induced by ouabain was not increased by incubation with [14C]DOPA instead of [14C]tyrosine. Ouabain-induced [14C]catecholamine formation was influenced by decreases in extracellular Ca2+ concentration, but not by the presence of cycloheximide or actinomycin D. These results suggested that ouabain stimulates continuous activation of hydroxylation of tyrosine through a Ca2+ -dependent mechanism in cultured bovine adrenal chromaffin cells.

Animals↗