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[Urinary excretion of catecholamines in the dog: physiopathologic hypotheses in man].

Renal handling of free catecholamines (dopamine, norepinephrine and epinephrine) was studied in 36 hydropenic anesthetized mongrel dogs in accordance with the clearance technique. There was no statistically significant correlation between plasma concentrations and either systemic (mean blood pressure, or cardiac output) or renal (clearance of PAH or glomerular filtration rate) hemodynamics. Net tubular transport (NTT) was calculated as the difference between filtered load and urinary excretion for any catecholamine. The mean NTTs of free catecholamines were as follows: --2,72 ng/min for dopamine, --3,18 for norepinephrine, and --1,36 for epinephrine, showing that they are mostly reabsorbed. However the use of averages is misleading inasmuch as tubular transport of free catecholamines is a heterogeneous phenomenon: a secretion appears to predominate when plasma concentrations are low and a reabsorption predominates when they are high. Whether such a heterogeneity is due to either a genetic heterogeneity in mongrel dogs, or an age-related difference is discussed.

Animals↗

Fetal catecholamine release in response to labor and delivery.

Umbilical arterial plasma norepinephrine and epinephrine were measured using a sensitive, specific radioenzymatic assay. Plasma catecholamines were correlated with umbilical arterial blood gases, durations of the first and second stages of labor, duration of rupture of the membranes, fetal heart rate tracings, and fetal sex. Significant correlations were observed for plasma norepinephrine versus fetal pH and PO2 and plasma epinephrine versus pH but not PO2. The majority of the fetal heart rate tracings demonstrated either a normal baseline or mild variable decelerations. The plasma catecholamines and blood gases were similar in these 2 groups. Significant elevations of both plasma catecholamines were observed with those tracings commonly associated with fetal distress; however, the number of infants was small. No sex differences were observed in plasma norepinephrine or epinephrine or in responsiveness. The results suggest that the human fetus at term responds to acidosis and hypoxia with a graded catecholamine release. This may be an important adaptive mechanism.

Adult↗

Biochemical genetics of catecholamines in humans.

Studies of the effects of inheritance on human catecholamine biosynthetic and metabolic enzymes are reviewed. Genetic polymorphisms have been shown to control the level of the biosynthetic enzyme dopamine beta-hydroxylase in serum and the level of the metabolic enzyme catechol-O-methyltransferase in a variety of tissues. Platelet monoamine oxidase, another catecholamine metabolic enzyme, is also under genetic control. These observations help to explain individual differences in response to treatment with catechol drugs and may explain some variations in the function of human catecholamine neurotransmitters. The biochemical genetic approach used to study the enzymes of catecholamine biosynthesis and metabolism could be used to investigate other aspects of adrenergic function and could serve as a model for studies of the effects of inheritance on other human neurotransmitter systems.

Blood Platelets↗

[Role of catecholamines in the biochemical mechanisms of the pathogenesis of hepatocerebral dystrophy].

In 48 patients with hepatocerebral dystrophy the principal parameters of the catecholamine metabolism were examined. Pronounced changes characterized primarily by a considerable diminution of dopamine and noradrenaline excretion and an increase of the excretion of their immediate precursor, i.e. DOPA, were noted. On the basis of the data obtained it was assumed that the synthesis of these neurotransmitting catecholamines was depressed. In the course of treatment with d-penicillamine which is capable of mobilizing copper and stimulating its excretion from the body a statistically significant increase of the dopamine excretion (as compared with its initial level) was noted, and in patients with the graver rigid-arrhythmohyperkinetic form of the disease the excretion of not only dopamine, but also noradrenaline, was increased. It is supposed that the disturbances of catecholamine metabolism in hepatocerebral dystrophy have a complicated mechanism, and are associated with both the grave hepatic pathology and disturbances of copper metabolism. In this connection additional methods of treating that disease are offered. These methods influence catecholamine metabolism, and act primarily on extrapyramid motor, and also psychic disorders. The studies carried out by the author make a contribution to the existing concepts of the biochemical mechanisms of the hepatocerebral dystrophy pathogenesis, and expand the possibilities of treating the grave hereditary disease.

Adolescent↗

Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats.

We have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure.

Animals↗

[Plasma catecholamines and hemodynamics in left heart failure (author's transl)].

7 healthy male subjects, 17 patients with left heart failure of degree I and II and 14 patients of degree III and IV (3 patients) based on a coronary heart disease were examined at rest and during ergometric exercise in supine position during a right-heart-catheter examination. Three patients degree IV were not exercised. Compared to healthy subjects, the patients showed, according to disease severity, catecholamine level increases at rest and at the same submaximum exercise intensity. The catecholamine levels show no difference between the patients and healthy subjects during maximum ergometric exercise, although the patients exercise load was 30% (degree I and II) and 60% (degree III) lower. Three patients of the degree IV already have plasma catecholamine levels at rest like those of healthy subjects during maximum ergometric exercise at 155 +/- 33 Watts. Adrenaline and noradrenaline show a direct correlation to pressure dimensions as to the PCPm or the PAPd corresponding to the limitation extent of cardiac function. Estimation of plasma catecholamines in left heart failure during ergometric exercise allows an orientational judgement of the course of hemodynamic dimensions such as PCPm, PAPd and HMV without renewed invasive diagnostic.

Catecholamines↗

Differential assay for urinary catecholamines by use of liquid chromatography with fluorescence detection.

I describe a relatively simple and rapid procedure for quantitative analysis for unconjugated urinary norepinephrine, epinephrine, and dopamine. Catecholamines are isolated from urine on a carboxylic acid ion-exchange resin (Bio-Rex 70) and eluted with 0.8 mol/L boric acid. The eluates are assayed for the individual catecholamines by "high-performance" liquid chromatography with an octadecylsilane reversed-phase column and 10 mmol/L perchloric acid-acetonitrile (99/1) as the mobile phase. The catecholamines are detected by measuring their intrinsic fluorescence on excitation at 200 nm. The method is highly reproducible, the coefficient of variation for normal concentrations in urine being 4.4% for norepinephrine, 8.8% for epinephrine, and 4.8% for dopamine. Moreover, it appears to be practically free of interference by drugs or endogenous compounds in urine. The range of catecholamine concentrations found in 143 hypertensive patients agrees well with previous studies.

Catecholamines↗

Effects of chronic treatments upon the brown adipose tissue of rats. II. Comparison between the effects of catecholamine injections and cold adaptation.

The role of noradrenaline in the trophic response of brown adipose tissue (BAT) to chronic and cold exposure was studied in young adult rats treated chronically with catecholamines. 2 In young rats, it was difficult to induce a BAT development with this type of treatment. After injection of a beta-agonist (isopropylnoradrenaline) directly upon BAT, a slight hypertrophy of the tissue was observed accompanied by a decrease of its relative protein content. 3 In adult rats, catecholamines were able to induce a growth of BAT and increases of the DNA and protein contents which were as great as in the BAT of cold-exposed rats. 4 Catecholamine treatments did not reproduce the effects of cold exposure on the phospholipids of BAT in either young or adult rats. 5 In the BAT of rats receiving chronically thyroxine and catecholamines, no synergy was observed. Moreover, a chronic treatment by thyroxine induced a slight increase of the DNA content of BAT in rats bred at room temperature, but prevented the marked DNA increase observed in cold-exposed animals.

Adaptation, Physiological↗

[Dynamics of levels of growth hormone and free fatty acids in the blood, and catecholamines in the urine of insulin-resistant and insulin-sensitive diabetes mellitus patients during insulin hypoglycemia].

The changes in the content of STH and FFA in the blood and of catecholamines in the urine under the effect of insulin hypoglycemia were studied in 28 insulin-sensitive and 40 insulin-resistant patients suffering from diabetes mellitus. Patients with diabetes mellitus who needed 100 or more insulin units per 24 hours for compensation of the affection were referred to the insulin-resistant ones. In these cases a less pronounced elevation of the blood STH level and of urinary catecholamines was noted in response to insulin hypoglycemia. This was accompanied by a considerable reduction of lipolysis in the insulin-resistant patients. It is suggested that in the insulin-resistant patients, due to reduction of the STH and catecholamine stimuli, FFA is incapable of providing the necessary energy balance at the cellular level in insulin insufficiency. This accounts for an increased requirement in exogenous insulin in the insulin-resistant patients with diabetes mellitus. Reduction of the FFA and catecholamine reserves in the insulin-resistant patients suffering from diabetes mellitus is postulated to be one of the main factors in the resistance pathogenesis.

Adolescent↗

[Various characteristics of catecholamine metabolism in thyrotoxicosis].

Catecholamine metabolism was studied and compared with thyrotoxicosis in 205 patients, depending on the age, illness severity and therapy type. Analysis of the data obtained allowed one to observe some peculiarities of catecholamine metabolism in thyroid hyperfunction: i. e. biosynthesis inhibition and catecholamine metabolism intensification, shunting of these monoamine metabolic changes from oxidative deamination to O-methylation with simultaneous H- and O-methylation growing. The role of thyroid hormones in catecholamine biosynthesis and metabolic deactivation was proved. Such an effect on thyroid hormones is estimated as a reaction, promoting inhibition of the sympathycoadrenal system functional activity.

Catecholamines↗

The organisation of catecholamine-containing neurons in the brain of the rhesus monkey (Macaca mulatta).

The distribution of catecholamine neurons in the brains of several rhesus monkeys (Macaca mulatta) was studied by means of the Falck-Hillarp formaldehyde histofluorescence technique. Catecholamine-containing cell bodies in the medulla and pons were found to correspond essentially to the noradrenaline cell groups A1-A7, originally defined in the rat. The pontine catecholamine neurons of the locus coeruleus (A6) and subcoeruleal tegmental areas (A6, A5 and A7) are, however, far more numerous in M. mulatta; observations which agree with reports in other primate species and carnivores. Rostrally projecting fibres, analogous to the ascending 'ventral' and 'dorsal' noradrenaline bundles described in other species, have also been observed in addition to those equivalent to the dorsal periventricular system. The large number of cells present throughout the mesencephalon represent dopamine cell groups A8-A10, while small populations of catecholamine neurons within the periventricular regions of the hypothalamus correspond to groups A11-A14. A prominent terminal innervation of the diencephalon (hypothalamus) is also evident in M. mulatta. Although similar in general terms to that in other species, several important variations are apparent. These and other differences noted above may underlie species specific variations in behaviour.

Animals↗

[Study of the catecholamines in the notochord of Anura Amphibia embryos. Its possible relationships with the adenyl-cyclase activity and the primordial germ cells migration (author's transl)].

Notochord from several Anura Amphibia embryos was investigated by cytochemical study. A green fluorescence was observed, indicating a catecholamine storage in the notochord, during a precise time of their development. A stimulation of the mesoblast area by catecholamine is suggested by the analogy between the catecholamine chordal distribution and the adenyl-cyclase activity of the chordo-mesoderm. This stimulation would be followed by a cAMP production directing the PGC migration. Treatment by L-dopa increases fluorescence in the notochord. Reserpine and alpha-methyl-paratyrosine decreases the notochord fluorescence, either by stocked catecholamine depletion in the case of reserpine, or by inhibition of their synthesis by alpha-methyl-para-tyrosine.

Adenylyl Cyclases↗

[Circadian rhythm of free catecholamine excretion in disturbed adrenal function (author's transl)].

The daily time course of urinary catecholamine excretion was determined for hyperactivity of the sympathoadrenal system (3 phaeochromocytomas, 1 neuroblastoma), disturbed adrenal function (M. Addison and partial adrenal insufficiency), bilateral adrenalectomy (one patient), in 8 healthy patients receiving dexamethasone, and in a control group. All groups showed a circadian rhythm of catecholamine excretion. In the patients with phaeochromocytoma, the excretion of catecholamines and vanilmandelic acid showed a shift of phase compared with the control group. In patients with hyperfunction of the sympathoadrenal system, catecholamines and vanilmandelic acid fluctuated with similar amplitudes, whereas in healthy patients vanilmandelic acid and dopamine showed much smaller fluctuations of concentration than adrenaline and noradrenaline.

Adrenal Gland Diseases↗

[Comparison between the treadmill exercise test and atrial stimulation with measurements of plasma catecholamines in patients with angina pectoris].

The assessment of atrial pacing (AP), in relation to the electrocardiographic treadmill test (ETT), was carried out in 22 patients with angina pectoris in whom the importance of the adrenergic system was also evaluated. Coronary cineangiography, left ventricular angiography and plasmatic catecholamine determinations were carried out before and after ETT and transvenous AP. All patients with coronary artery obstruction of more than 80% had positive ETT (X2 = 5.2) and 61.5% had positive AP tests (X2 = 5.2) and 61.5% had positive AP tests (X2 = 3.16). Sixty six of those patients without angiographic coronary obstruction had positive ETT and in 55.6% the AP test was also positive. The increase in systolic blood pressure was found to correlate with the increase in plasmatic catecholamine concentrations during ETT but not with AP (p less than 0.001). The electrocardiographic treadmill test has a greater specificity and sensitivity than AP and correlates with the plasmatic catecholamine concentration. Our results suggest that the myocardial ischemia produced by AP is not related to the endogenous output of catecholamines nor to the elevation of blood pressure, but rather it seems to be dependent of a greater imbalance between the cardiac debit supply ratio of oxygen induced exclusively by an increase in heart rate.

Adult↗

Evaluation of a radioenzymic kit for determination of plasma catecholamines.

We evaluated a commercially available reagent test-kit (Upjohn) for simultaneously determining norepinephrine, epinephrine, and dopamine in 50-microL of plasma. The three catecholamines are enzymically converted into the radioactive O-methyl derivatives and separated by thin-layer chromatography. Day-to-day precision (CV) was 11, 10, and 14% for norepinephrine, epinephrine, and dopamine, respectively. The relationship between concentration of catecholamine and radioactivity (net dpm) was linear to at least 8 ng (corresponding to 1 mumol/L in plasma). Sensitivity was approximately 2 pg for dopamine, 1 pg for each of the other two catecholamines. Under our conditions, epinephrine was not quite completely resolved from the other two fractions. Catecholamine values determined in normal humans, after 30 min supine and after normal laboratory activity, agreed well with those found by other investigators. Correlation was good between kit results and those obtained in another laboratory that used self-prepared reagents and "high-performance" liquid chromatography for the separation.

Catecholamines↗

A sensitive method for determination of conjugated catecholamines in blood plasma.

Conjugated catecholamines in blood plasma of blood donors were determined from the difference between the total and the free catecholamines. Total catecholamines were measured after complete hydrolysis of the conjugated amines (heating of acidified samples for 40 min at 95 degrees C). Free catecholamines were determined in untreated plasma. Determinations were performed radioenzymatically. We combined and modified the procedures of Peuler & Johnson (1977) Life Sci 21, 625-636) and Da Prada & Zürcher (1976) Life Sci 19, 1161-1174). The resulting method was less laborious and cheaper.

Adult↗

[Plasma catecholamine content in hypertensive subjects and spontaneously hypertensive rats using radioenzymatic assay (author's transl)].

The present experiments were undertaken to determine the plasma catecholamine content in normotensive, slightly hypertensive humans and spontaneously hypertensive rats using radioenzymatic assay. In addition, attempts were made to compare radioenzymatic assay with a fluorometric technique, using high performance liquid chromatography with respect to human plasma catecholamine content. Human plasma catecholamine content in normotensive subjects at rest was 250 +/- 61 pg/ml (mean +/- S.E.) for norepinephrine and 37 +/- 22 for epinephrine. Immediately after treadmill exercise, human plasma norepinephrine content significantly increased. In 14 patients with mild essential hypertension, plasma norepinephrine was 460 +2- 128 pg/ml with the subject in a supine position and 1030 +/- 151 in the case of treadmill exercise. Thus, there was a statistically significant difference. With regard to plasma catecholamine content in spontaneously hypertensive rats, the norepinephrine content was 816 pg/ml, epinephrine was 209 pg/ml and dopamine was 505 pg/ml, on an average. After comparing this method with the fluorometric technique using high performance liquid chromatography, we confirmed that the former requires much smaller sizes of samples and has much the same sensitivity as the latter.

Adult↗

[Effect of prednisolone on 3H-catecholamine synthesis in the adrenals of physically fatigued rats].

The effect of prednisolone on the synthesis of 3H-catecholamines by the adrenals of control and rats swimming for 8 hours was studied in experiments in vitro with the use of 3H-thyroxine as precursor. It was shown that in swimming rats, the synthesis of 3H-noradrenaline and 3H-adrenaline is inhibited by 25%, while the synthesis of 3H-dopamine remains unchanged. Addition of prednisolone to the incubation medium does not affect the rate of 3H-catecholamine synthesis by the adrenals of intact rats. Addition of prednisolone to the adrenals of swimming rats leads to the stimulation of the synthesis of 3H-noradrenaline and 3H-adrenaline by 72%, while the synthesis of 3H-dopamine gets stimulated by 56% relative to the synthesis rate of 3H-catecholamines during swimming. In the latter case the rate of 3H-catecholamine synthesis significantly exceeds the control level.

Adrenal Glands↗