THE FEATURES OF THE WOMEN'S SIMPATHOADRENAL SYSTEM FUNCTIONAL STATE WITH RISK OF EARLY PREGNANCY TERMINATION.

Preterm labor is an urgent medical-social and demographic issue at the present stage. A considerable number of factors affects the course of pregnancy and its outcome, their effect is realized at the level of the central nervous system through numerical metabolic interactions, where monoaminergic systems play an important role. Objective - to study the features of the sympathoadrenal system state by determining the excretion level of DOPHA, dopamine, norepinephrine and epinephrine in women's daily urine with different periods of abortion. 227 pregnant women who were admitted to the Kharkiv perinatal center have been examined, 190 of them had clinical signs of premature delivery in the gestation period of 23-36 weeks. Formation of clinical groups was carried out depending on the pregnancy term in the form of premature and timely delivery. Diagnosis of preterm labor was carried out in the presence of abdominal pain syndrome and structural changes in the cervix. Consequently, pregnancy compensatory and adaptive mechanisms are complex of neurohumoral process, which are realized through monoaminergic systems and a significant factor in its interruption is their destabilization. Reducing of sympathoadrenal system activity and reserve capacity in pregnant women may be a pathogenetic factor in the development of preterm labor. Therefore determination of the imbalance initial manifestations in the catecholamines exchange may possibly prevent the loss of pregnancy in the early stages.

An increase in renal dopamine does not stimulate natriuresis after fava bean ingestion.

BACKGROUND: Fava beans (Vicia faba) contain dihydroxyphenylalanine (dopa), and their ingestion may increase dopamine stores. Renal dopamine regulates blood pressure and blood volume via a natriuretic effect. OBJECTIVE: The objective was to determine the relation between dietary fava beans, plasma and urinary catechols, and urinary sodium excretion in 13 healthy volunteers. DESIGN: Catechol and sodium data were compared by using a longitudinal design in which all participants consumed a fixed-sodium study diet on day 1 and the fixed-sodium diet plus fava beans on day 2. Blood was sampled at 1, 2, 4, and 6 h after a meal, and 3 consecutive 4-h urine samples were collected. RESULTS: Mean (±SD) plasma dopa was significantly greater 1 h after fava bean consumption (11,670 ± 5440 compared with 1705 ± 530 pg/mL; P = 0.001) and remained elevated at 6 h. Plasma dopamine increased nearly 15-fold during this period. Fava bean consumption also increased urinary dopamine excretion to 306 ± 116, 360 ± 235, and 159 ± 111 µg/4-h urine sample compared with 45 ± 21, 54 ± 29, and 44 ± 17 µg in the 3 consecutive 4-h samples after the control diet (P ≤ 0.005). These substantial increases in plasma and urinary dopa and dopamine were unexpectedly associated with decreased urinary sodium. CONCLUSION: The failure of fava bean consumption to provoke natriuresis may indicate that dopa concentrations in commercially available beans do not raise renal dopamine sufficiently to stimulate sodium excretion, at least when beans are added to a moderate-sodium diet in healthy volunteers. This trial was registered at clinicaltrials.gov as NCT01064739.

[Catecholamine metabolism in different forms of Parkinson's disease]. / Obmen katekholaminov pri raznykh formakh bolezni Parkinsona.

Catecholamine metabolism was evaluated by daily urine excretion in patients with Parkinson's disease of tremor (18 patients) and rigid (14 patients) types. The group included 16 untreated patients. According to urine analysis, most informative peripheral markers for dopamine metabolism proved to be DOPA excretion, 3,4-dioxyphenylacidic acid (DOPAA) level and DOPA/DOPAA ratio. In the initial disease stage, a marked decrease of free dopamine and noradrenaline as well as dopamine metabolism intensification with corresponding DOPA/DOPAA ratio decrease were found. Significantly lower DOPAA and DOPA excretion was detected in patients with predominance of akinesia and rigidity types compared to tremor ones. In contrast to untreated patients, those treated with drugs containing dopamine revealed correlations between daily urine DOPA excretion as well as DOPA/DOPAA ratio with neurological symptoms severity.

Evaluation of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma 3,4-dihydroxyphenylalanine (DOPA) as tumor markers in children with neuroblastoma.

Catecholamines and their metabolites are important in the diagnosis of neuroblastoma (NB). Plasma (p-) levels of 3,4-dihydroxyphenylalanine (DOPA) are increased in most NB, probably reflecting decreased DOPA decarboxylase activity. Urine (u-) homovanillic acid (HVA), a DOPA and dopamine (DA) metabolite. is also increased in most NB. DOPAC (3,4-dihydroxyphenylacetic acid) is an important metabolite of DA in tissues with monoamine oxidase (MAO) activity. Because MAO is expressed in NB tumor cells, we studied the importance of measuring p-DOPAC and p-DOPA as compared to u-HVA and u-vanillylmandelic acid (VMA) in the diagnosis and follow-up of NB. DOPAC, DOPA, dopamine, noradrenaline, adrenaline, VMA and HVA were measured by reverse-phase HPLC with electrochemical detection in 106 children (28 with NB (13 newly diagnosed), 25 with other solid tumors, 28 hospitalized for nonneoplastic diseases, and 25 healthy children). P-DOPAC or p-DOPA concentrations were above the upper normal range in 92% of untreated NB patients, as were u-HVA or u-VMA levels. None of these tumor markers was correlated to tumor stage or survival. P-DOPA but not p-DOPAC was correlated to age in NB children. Increased values of p-DOPAC and p-DOPA were found in one patient surviving NB for 10 years. Plasma DOPAC concentrations were decreased in children hospitalized for non-NB diseases, probably reflecting reduced food intake. Plasma analyses of DOPA and DOPAC seem to be useful alternatives in the diagnosis and follow-up of NB if urine sampling is to be avoided. Plasma DOPAC may be an index of nutritional status in various diseases.

Effects of thyroid hormone on the renal dopaminergic system.

This study determined the effects of thyroid hormone on the renal dopaminergic system. Surgical thyroidectomy (Tx) and treatment with 2-thiouracil (Thio) decreased renal cortex Na+/K+ ATPase activity and urinary volume. Tx also decreased urinary Na+ and urinary L-DOPA without changing urinary excretion of Dopamine (DA). Thio treatment decreased slightly urinary L-DOPA and Na+, but increased urinary excretion of DA. In both models of thyroid hormone deficiency, the ratio urinary DA/DOPA increased. Changes after Thio treatment were reversed after one month of drug withdrawal. Treatment with T3 via osmotic minipump increased Na+/K+ ATPase activity and urinary L-DOPA, did not change urinary DA, and increased the ratio DA/DOPA. To further analyze the effects of thyroid hormone deficiency, we administered selective DA1 (SCH-23390), DA2 (Sulpiride), and a non selective (Haloperidol) DA receptor antagonists to Thio treated and control animals. The DA1 antagonist decreased diuresis, natriuresis and urinary L-DOPA in control, but had no effect in Thio treated rats. Sulpiride had no effect in either group. The combination of SCH-23390 plus Sulpiride decreased urinary L-DOPA and urinary volume only in Thio treated animals. Haloperidol decreased urinary volume in Thio treated animals, but had no effect in controls. Our findings suggest that renal DA synthesis is to some extent dependent on thyroid hormone levels, and that the response of DA receptors is altered by thyroid hormone deficiency, indicating a role of this hormone in the regulation of the renal dopaminergic system.

Dopamine and dopa urinary excretion in patients with pheochromocytoma--diagnostic implications.

Pheochromocytoma, a potentially life-threatening disease, is a rare cause of hypertension. Most pheochromocytomas secrete excessive amounts of noradrenaline and adrenaline. It has been suggested by some authors that high circulating levels of dopamine and the catecholamine precursor dihydroxyphenylalanine (dopa) are more often associated with malignant rather than benign pheochromocytomas. Therefore the aim of this study was to evaluate urinary excretion of dopamine and dopa in patients with pheochromocytoma and to determine their role as a potential marker for malignancy of the tumour. We retrospectively analysed 120 consecutive patients (mean age 41 +/- 12 years) with histopathologically confirmed pheochromocytomas. All subjects were divided as follows: group 1 included patients with both elevated and normal dopamine urinary excretion; group 2 was characterized by increased and normal dopa urinary excretion. Dopamine urinary excretion was increased in all patients with malignant pheochromocytoma, but higher levels were also observed in some patients with a benign tumour included in group 1. Urinary excretion of dopa was in the normal range in all subjects with malignant pheochromocytoma. The results indicate that in some pheochromocytoma patients excessive dopamine excretion may point to malignant tumour, but is not a discriminating marker for malignancy in the whole studied group.

[Effects of bromantane and sidnocarb on long-term operant conditioning and its vegetative correlates in rats]. / Vliianie bromantana i sidnokarba na éffektivnost' dlitel'noi operantnoi deiatel'nosti i ee vegetativnye korreliaty u krys.

Bromantan (20 mg/kg, p.o.) and sydnocarb (10 mg/kg, p.o.) augment the efficacy of a 5-h operant activity in rats, the effect being achieved through different pathways. Sydnocarb increases the number of operant reactions and exhausts the sympathico adrenal system reserves. Bromantan favors the activity optimization by reducing the number of errors at a smaller number of operant reactions. Bromantan increases the tension of motivational component (electric pain irritation avoidance), whereas sydnocarb decreases this component of the operant behavior. None of the two drugs affects the degree of functional activation of the cardiovascular system.

Catecholamines and their metabolites in the brain and urine of rats with experimental Parkinson's disease.

The content of catecholamines and their metabolites in the brain and the relationship between cerebral catecholamine levels and their urinary excretion were studied in rats with 6-OHDA-induced hemiparkinsonism. 6-OHDA reduced brain concentrations of dopamine, DOPAC, and homovanilic acid and urinary excretion of dopamine, dioxyphenilalanine, and DOPAC by more than 90%. A positive correlation was found between the concentrations of these metabolites in the urine and striatum. Measurement of urinary catecholamines and their metabolites is a perspective test for evaluating the status of the dopaminergic nigrosostriate system of the brain in experimental parkinsonism.

Effect of glucocorticoids on renal dopamine production.

This study assess the effects of glucocorticoids on dopamine excretion and evaluates the participation of renal dopamine in the effects of glucocorticoids on renal function and Na+ excretion. Dexamethasone (i.m.; 0.5 mg/kg) was administered to male Wistar rats on day 2 or on days 2 and 5. Daily urinary excretions of Na+, dihydroxyphenylalanine (DOPA), dopamine and dihydroxyphenylacetic acid were determined from day 1 to day 7. Renal function was evaluated 8 h after dexamethasone administration in a separate group. The first dose of dexamethasone increased about 100% diuresis and natriuresis, increased urinary DOPA and renal plasma flow, and did not affect urinary dopamine or the other parameters evaluated. These effects were not affected by previous administration of haloperidol. The second dexamethasone dose increased about 200% diuresis and natriuresis, increased urinary dopamine, DOPA, dihydroxyphenylacetic acid, Uosm x V and both glomerular filtration rate and renal plasma flow. Carbidopa administered before the second dexamethasone dose blunted both the diuretic and the natriuretic response whereas haloperidol abolished or blunted all the effects of the second dexamethasone dose. These results show that modifications in renal dopamine production produced by corticoids may contribute to the effects of these hormones on Na+ balance and diuresis and suggest that regardless the factor that promotes an increase in renal perfusion and glomerular filtration rate during long term administration of glucocorticoids, a dopaminergic mechanism is actively involved in the maintenance of these hemodynamic changes.

Generalized melanosis in metastatic malignant melanoma: the possible role of DOPAquinone metabolites.

Generalized melanosis occurs very rarely as a complication of malignant melanoma, and the pathogenesis of this condition is still unclear. Histological examination of pigmented skin and measurements of the DOPAquinone metabolites 5-S-cysteinyldopa (5-S-CD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) in the patient's serum and urine were carried out. Histological examination revealed basal hyperpigmentation, discrete melanoma cells and melanophages around the blood vessels and an unusual melanin deposition within collagen bundles in the dermis. The levels of 5-S-CD and 6H5MI2C were dramatically increased both in the patient's serum and urine. The deposition of DOPAquinone metabolites secreted by the melanoma cells may contribute to the unusual melanin deposition within collagen bundles in the affected dermis.

[Evaluation of the usefulness for measuring catecholamines and their principle metabolites in the diagnosis of pheochromocytoma]. / Ocena przydatnosci oznaczania katecholamin i ich glównych metabolitów w diagnostyce guzów chromochlonnych.

Objective of the study was assessment of the usefulness of determination of noradrenaline (NA) and adrenaline (A) in urine and blood as well as the total methoxycatecholamines (MNA +MA), vanillylmandelic acid (VMA), DOPA and dopamine (DA) urinary excretion in diagnosis of pheochromocytoma. The experience based on 155 patients with pheochromocytoma (105F, 50M, age 18-82 yrs) diagnosed in the Department of Hypertension and Angiology Academy of Medicine in Warsaw will be discussed. In all patients excluding 2 cases pheochromocytoma has been proven histopathologically. The most considerable diagnostic usefulness of MNA + MA indication was proven. MNA + MA was increased in 96.6 patients. In 89.6% patients an increased excretion of NA and A or one of this catecholamines was demonstrated. An increased excretion of VMA was demonstrated in 75%. The excretion of DOPA and dopamine was tested in 120 cases. An increased excretion of DA was shown in 31% and DOPA in 16%.

High sodium intake increases the urinary excretion of L-3,4-dihydroxyphenylalanine but fails to alter the urinary excretion of dopamine and amine metabolites in Wistar rats.

1. The present study has examined the daily urinary excretion of L-DOPA, dopamine and its metabolites (DOPAC, 3-MT and HVA) during normal salt (NS) and high salt(HS) diets. 2. Daily urinary excretion of L-DOPA, DA, DOPAC, 3-MT and HVA during the 4-day period of NS diet averaged, respectively, 7.6 +/- 0.4, 71 +/- 5, 217 +/- 22, 570 +/- 90 and 1217 +/- 110 nmol/kg/day. The slight increase in the urinary excretion of DA, DOPAC and 3-MT (16% to 42% increase), when rats were fed a HS diet, did not achieve statistical significance. 3. In contrast, the urinary levels of L-DOPA during the HS diet period (11 +/- 1 nmol/kg/day) were found to be significantly higher than during the NS diet period; the maximal increase in the urinary excretion of L-DOPA (93% increase) was observed in the first day and then a progressive decline was observed towards the end of the HS intake period. 4. During the first 5 days of the HS intake period, the urine output of noradrenaline (NA) was found to increase (27% to 83%) and then to progressively decline to baseline values (13.5 +/- 0.7 nmol/ kg/day). Urinary excretion of adrenaline (AD) during the HS intake period was found to increase (72% to 146%); the mean daily urinary excretion of AD during the NS diet period averaged 2.5 +/- 0.4 nmol/ kg/day. NS and DA contents in the kidney of rats on a NS diet were not significantly different from that of rats in a HS diet. 6. It is concluded that long-term HS intake in Wistar rats fail to change the urinary excretion of DA and of its metabolites (DOPAC, 3-MT and HVA). Furthermore, the discrepant profile in the urinary excretion of L-DOPA and DA during HS intake might be related to a reduction in the tubular uptake of the amino acid, rather than reflecting a decrease in its decarboxylation.

Urinary catecholamine excretion and behavioral differences in ADHD and normal boys.

Urinary catecholamine excretion was assessed in 15 boys with attention-deficit/hyperactivity disorder (ADHD) and 16 normal controls during a defined physical and mental task. Dihydroxyphenylalanine, dopamine, norepinephrine (NE), epinephrine (EPI), 3,4-dihydroxyphenylacetic acid, and 3,4-dihydroxyphenylglycol (DOPEG) concentrations were assayed by high-pressure liquid chromatography with electrochemical detection. The urinary concentration of DOPEG, an NE metabolite that has not been previously measured in ADHD, was significantly lower in the ADHD subjects than in the normal controls. There was also a trend for lower urinary EPI levels in the hyperactive boys. Stepwise multiple regression analyses demonstrated that DOPEG and EPI each contributed significantly to the variance in the behavioral symptoms within the full sample. The results are consistent with previous reports of abnormal metabolism of norepinephrine and epinephrine in ADHD. These neurochemical findings may be due to differences between ADHD and normal boys in neuronal (central or peripheral) or nonneuronal (e.g., adrenal, renal) activity. The results are also consistent with prior findings in normal children of an inverse relationship between EPI excretion and inattentive, restless behaviors. Together, these findings suggest caution in ascribing metabolite changes to ADHD or to ADHD-like behaviors that may be seen in normal children.

Antagonistic actions of renal dopamine and 5-hydroxytryptamine: endogenous 5-hydroxytryptamine, 5-HT1A receptors and antinatriuresis during high sodium intake.

1. The present study has examined the effect of (+)-WAY 100135, a selective antagonist of 5-HT1A receptors, and ketanserin, an antagonist of 5-HT2 receptors, on the urinary excretion of Na+, K+, dopamine, 5-hydroxytryptamine (5-HT) and their metabolites in rats treated with the selective type A monoamine oxidase (MAO-A) inhibitor, Ro 41-1049 (15 mg kg-1 day-1) in conditions of normal sodium (NS) and high sodium (HS; 1.0% NaCl in drinking water) intake. 2. Male Wistar rats were placed in metabolic cages and were given tap water (NS diet) in the first 4 days of the study and then challenged to a HS diet for another 7 days. Ro 41-1049 was given in drinking water only in the last 3 days of the HS diet, whereas (+)-WAY 100135 (5 and 10 mg kg-1 day-1, s.c.) or ketanserin (2 mg kg-1 day-1, s.c.) were administered in the last 4 days of the HS intake period. 3. Daily urinary excretion (in nmol kg-1 day-1) of dopamine (82 +/- 2), 3,4-dihydroxyphenylacetic acid (DOPAC; 198 +/- 9), homovanillic acid (HVA; 915 +/- 47), 5-HT (586 +/- 37) and 5-hydroxyindoleacetic acid (5-HIAA; 1035 +/- 64) in the HS intake period was similar or higher than that in NS diet (dopamine = 68 +/- 2, DOPAC = 197 +/- 4, HVA = 923 +/- 42, 5-HT = 539 +/- 132, 5-HIAA = 1286 +/- 95). The administration of Ro 41-1049 on 3 consecutive days reduced the urinary excretion of dopamine, DOPAC and HVA, respectively, by 35-51% (P < 0.05), 73-85% (P < 0.05) and 59-66% (P < 0.05); the urinary excretion of 5-HT increased 2 fold (P < 0.01) and the levels of 5-HIAA were reduced by 39-77% (P < 0.05). 4. During HS intake (7 days), daily urinary excretion of Na+ increased 5.5 fold (from 6.7 +/- 0.2 to 36.5 +/- 0.9 mmol kg-1 day-1), without changes in the urinary excretion of K+ (from 11.2 +/- 0.2 to 11.9 +/- 0.5 mmol kg-1 day-1) and urinary osmolality (from 1083.8 +/- 26.7 to 1117.7 +/- 24.1 mOsm kg-1 H2O). MAO-A inhibition during HS intake was found to produce a 47-68% decrease in Na+ excretion (from 39.1 +/- 0.7 to 15.1 +/- 2.5 mmol kg-1 day-1, n = 4; P < 0.02) and urine volume (from 160.4 +/- 3.3 to 43.8 +/- 9.0 ml kg-1 day-1, n = 4; P < 0.02) without changes in K+ (from 11.1 +/- 0.5 to 9.2 +/- 0.6 mmol kg-1 day-1, n = 4) and creatinine (from 29.1 +/- 2.3 to 28.4 +/- 2.1 mg kg-1 day-1) excretion; urine osmolality increased 2 fold (from 936.3 +/- 40.3 to 2210.7 +/- 157.4 mOsm kg-1 H2O, n = 4; P < 0.02). Administration of (+)-WAY 100135 (5 and 10 mg kg-1 day-1), but not of ketanserin (2 mg kg-1 day-1), was found to inhibit the antinatriuretic effect induced by Ro 41-1049 during HS intake. 5. It is suggested that MAO-A inhibition during HS intake leads to an increased availability of 5-HT in renal tissues, the effect of which is a decrease in the urinary excretion of Na+, involving the activation of tubular 5-HT1A receptors.

[Determination of free and conjugated catecholamines, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid in the urine and blood plasma by high pressure liquid chromatography]. / Opredelenie svobodnykh i kon'iugirovannykh form katekholaminov, 3,4-dioksifenilalanina, 3,4-dioksifeniluksusnoi kisloty v moche i plazme krovi s ispol'zovaniem vysokoéffektivnoi zhidkostnoi khromatografii.

A method for simultaneous measurement of free and conjugated forms of adrenalin, noradrenaline, dopamine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid in the blood plasma and urine by high-pressure liquid chromatography with electrochemical detector has been developed. The levels of the said substances in 36 normal volunteers and 20 patients with mental disorders are presented. Simultaneous measurements of excretion of free catecholamines and their conjugates permitted a more complete characterization of catecholamine metabolism, which is important for understanding the mechanisms of disorders in catecholamine system in various diseases.

Salt-sensitivity testing in patients with borderline hypertension: reproducibility and potential mechanisms.

We examined the reproducibility of dietary salt-sensitivity testing by studying the effects on blood pressure (BP) of low sodium intake (20 mmol/day) and high sodium intake (220 mmol/day) in 10 men with borderline hypertension on two separate occasions. A difference in mean arterial pressure of 8 mm Hg between the high salt and the low salt regimen was arbitrarily chosen to define salt sensitivity. In addition, the reproducibility of changes in renal haemodynamics and in humoral factors, such as plasma renin activity, plasma aldosterone, atrial natriuretic peptide and urinary dopa and dopamine excretion, on the alteration in sodium intake were studied. As far as changes in BP are concerned, there was perfect agreement between the two tests, because in the second investigation, all subjects were classified in the same category as before. The salt-induced changes in plasma atrial natriuretic peptide and in renal excretion of dopa (dihydroxyphenylalanine) and dopamine were repeatedly and consistently different between the salt-sensitive and the salt-resistant group. The study revealed no support for a role of renal haemodynamics or the renin-angiotensin-aldosterone system in the pathophysiology of salt-induced elevations of BP in salt-sensitive subjects.

Dopaminergic abnormalities in hypertension associated with moderate renal insufficiency.

To evaluate the additive effect of moderate chronic renal failure to the abnormal dopamine generation and action observed in stable hypertension, we investigated 22 age-matched patients with a comparable degree of hypertension with and without chronic renal failure. Both groups were compared with each other and with an age-matched control group after a single oral dose of dihydroxyphenylalanine (DOPA) while cardiorenal responses and DOPA, dopamine, and their metabolites were measured. The hypertensive patients with chronic renal failure shared with their hypertensive counterparts without chronic renal failure an impaired DOPA decarboxylation to dopamine. However, patients with chronic renal failure had decreased hemodynamic and normal natriuretic responses compared with the hypernatriuresis of hypertensive patients with normal renal function; patients with chronic renal failure had elevated basal plasma concentrations of DOPA and dopamine sulfates as well as increased plasma and urinary DOPA sulfate but blunted urinary dopamine sulfate increases after DOPA administration; they presented augmented plasma atrial natriuretic factor concentrations. Thus, hypertensive patients with moderate chronic renal failure exhibit a decreased hemodynamic responsiveness to DOPA administration-induced dopamine elevation but with the natriuretic effect of dopamine maintained (possibly because of its permissive interaction with increased atrial natriuretic factor levels). Hypertensive patients with chronic renal failure have a heightened DOPA and dopamine sulfoconjugating propensity. Dopamine sulfate attenuates the biologic action of free dopamine. This may contribute (possibly via glomerular hypertension and hyperfiltration due to decreased postglomerular vasodilation) to progressive hypertensive renal damage, particularly in groups predisposed to dopamine deficiency, such as diabetics, blacks, and the elderly.

Derivation of urinary dopamine from plasma dihydroxyphenylalanine in humans.

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spill-over) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 micrograms min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenyl-acetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 +/- (SEM) 0.01 to 0.14 +/- 0.03 nmol/min, t = 2.80, P < 0.02] and dopamine (from 1.03 +/- 0.19 to 1.30 +/- 0.28 nmol/min, t = 2.35, P < 0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Defective 3,4-dihydroxyphenylalanine decarboxylation to dopamine in hydralazine-treated hypertensive patients may be pyridoxine remediable.

The previously observed defective dopamine (DA) generation from 3,4-dihydroxyphenylalanine (DOPA) can also be seen in patients treated for many years by hydralazine. This may be due to a hydralazine-induced depletion of pyridoxine, an essential coenzyme of the aromatic L-amino acid decarboxylase (LAAD). Eleven hydralazine-treated stable essential hypertensive (EH) patients, initially found to have a defect in the DOPA decarboxylation to DA, tested by a single DOPA administration (500 mg, orally), were retested by the same test 4 days after pyridoxine pretreatment (100 mg/day) for data on blood pressure (BP), pulse rate, and renal and plasma catecholamines and their metabolites, as well as plasma atrial natriuretic factor (ANF), cyclic GMP (cGMP), plasma renin activity (PRA), and plasma aldosterone (PA). Initially, hydralazine-treated stable EH patients manifested, following DOPA administration, lower DOPA decarboxylation to DA than control subjects. Pyridoxine pretreatment accelerated DA generation from exogenous DOPA and attenuated the DOPA-induced increases in plasma and urinary DOPA and its metabolite 3-O-methyl-DOPA, but accentuated the increase in free DA and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while BP, ANF, cGMP, PRA, and PA remained unaffected. The DOPA-induced increments of urinary DA were, in contrast to plasma DA changes, blunted by pyridoxine pretreatment. The attenuation of the sodium excretion by pyridoxine pretreatment exceeded that of the DA excretion, suggesting that pyridoxine suppressed a natriuretic factor, other than ANF, or activated a sodium-retaining factor, other than renin or aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)