Urinary Excretion Of Free Dopamine Research Articles

Elevated Urinary Free and Deconjugated Catecholamines after Consumption of a Catecholamine-Rich Diet

The biochemical diagnosis of pheochromocytoma depends on the demonstration of elevated levels of catecholamines (i.e. epinephrine, norepinephrine, and dopamine) and their metabolites. The aim of the study was to determine the preanalytical influence of a catecholamine-rich diet on urinary free and deconjugated catecholamines in healthy volunteers with a highly specific and sensitive analytical technique. We conducted a crossover study involving 27 healthy adults in a specialist medical center. Subjects consumed catecholamine-rich nuts and fruits at fixed times on one day (about 35 micromol dopamine and 1 micromol norepinephrine) and catecholamine-poor products on another day. Urine samples were collected at timed intervals before, during, and after experimental and control interventions. We performed automated online sample preparation coupled to isotope-dilution mass spectrometry measurements of urinary concentrations of free and deconjugated catecholamines. The catecholamine-rich diet had substantial effects on urinary excretions of deconjugated dopamine (up to 20-fold increases) and norepinephrine (up to 10-fold). Dietary catecholamines had less but significant effects on urinary excretion of free dopamine and norepinephrine (up to 1.5-fold increases). Outputs of urinary free and deconjugated epinephrine remained unaffected. Urinary excretion of deconjugated norepinephrine and dopamine is strongly affected by consumption of catecholamine-rich food products, thereby increasing the likelihood of a false-positive test result during hormonal evaluation for pheochromocytoma. Measurement of deconjugated catecholamines should therefore preferably be avoided, in favor of measurement of urinary free catecholamines. In case of demonstrating increased urinary excretion of deconjugated norepinephrine and dopamine, repeated measurements are warranted with dietary restrictions prior to sample collection.

Roles of renal dopamine and kallikrein-kinin systems in antihypertensive mechanisms of exercise in rats.

We have previously shown that both renal dopamine (DA) and kallikrein-kinin systems are activated by exercise in mild hypertensives. We aimed to confirm the effects of exercise on the renal DA system and the stimulatory effects of DA on the renal kallikrein-kinin system in rats. In experiment 1, 12 male Dahl salt-sensitive (DS) rats given a 4% salt diet were divided into two groups. Rats in the exercise group were forced to run at 8 m/min, 60 min/day, 5 days/week for 4 weeks. Daily urinary volume, urinary excretion of sodium, free DA, and kallikrein activity were measured weekly. Renal aromatic-L-amino-acid decarboxylase (AADC) activities were assayed at the end of the experiment. In experiment 2, 15 male Sprague-Dawley (SD) rats were randomly divided into 3 groups, a DA-5 (5 microg of DA/kg/min), a DA-10 (10 microg of DA/kg/min), and a control group. DA or vehicle was administered subcutaneously with an osmotic pump for 2 weeks. Daily urinary volume, urinary excretion of sodium, aldosterone, DA, and kallikrein activity were measured weekly. Plasma renin activity, aldosterone concentration, and renal kallikrein mRNA levels were determined at the end of the experiment. In experiment 1, urinary excretion of free DA and renal AADC activities in the exercise group were significantly higher than those in the non-exercise group at week 4. In experiment 2, renal kallikrein mRNA levels and urinary volume were significantly increased in the DA-10 group compared to the control group, although there were no differences in urinary kallikrein activities. Plasma aldosterone concentration was significantly decreased in the DA-10 group compared to that in the control group despite a lack of differences in plasma renin activities. In conclusion, exercise increased the urinary excretion of free DA, probably through increased renal AADC activity in DS rats. DA amplified renal kallikrein mRNA levels and decreased plasma aldosterone levels, probably through its suppression of aldosterone in the adrenal glands. Activation of the kallikrein-kinin system might be counteracted by post-transcriptional modification of aldosterone. These results suggest that exercise enhances renal dopamine production by activating renal AADC activity, which in turn stimulates the renal kallikrein-kinin system.

Changes of urinary dopamine excretion early after balloon mitral commissurotomy in mitral stenosis.

1. In order to investigate the changes of reduced urinary free dopamine excretion (uDA) in heart failure, 15 patients with symptomatic mitral stenosis were investigated on their uDA, endogenous creatinine (Cr) clearance, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline (pNA) and plasma L-dopa concentration before and early after percutaneous transvenous mitral commissurotomy (PTMC) by the clearance study. The delivery of L-dopa to renal proximal tubules (plasma L-dopa x Cr clearance), and the conversion ratio of plasma L-dopa to urinary dopamine in the kidney [uDA/(plasma L-dopa x Cr clearance)] were also estimated. 2. After successful PTMC, uDA, UNaV and FENa showed a significant but incomplete improvement and the changes of uDA were correlated positively with those of cardiac index (CI) (r = 0.665, P < 0.01), not with changes of pulmonary wedge pressure. While plasma L-dopa and plasma L-dopa x Cr clearance improved, uDA/(plasma L-dopa x Cr clearance) was not significantly changed early after PTMC. 3. From these results, it was suggested that reduced uDA tended to increase incompletely in relation with functional recovery of heart, and that increased plasma L-dopa and a delivery of L-dopa to renal proximal tubules have some positive role on urinary dopamine excretion, at least, early after PTMC.

Differential catecholamine responses to protein intake in healthy and hypertensive subjects.

Protein intake-induced natriuresis previously related to increased urinary dopamine excretion was reexamined in an extensive controlled study comparing healthy and hypertensive subjects. In healthy subjects, ingestion of 1 g/kg wt tuna induced natriuresis that was associated, between postprandial hours 1 and 2, with increased plasma tyrosine [191 +/- 13% (mean +/- SE); P < 0.01], 3, 4-dihydroxyphenylalanine (104 +/- 12%, P < 0.05 in plasma; 162 +/- 20%, P < 0.05 in urine), plasma free dopamine (156 +/- 32%; P < 0. 05), and dopamine sulfate (191 +/- 11%, P < 0.001 in plasma; 199 +/- 15%, P < 0.01 in urine) but affected urinary free dopamine excretion only at limits of significance. Hypertensive subjects had less (P < 0.02) natriuresis and, despite comparable plasma tyrosine and dopamine sulfate increases, no increase in plasma and urinary 3, 4-dihydroxyphenylalanine and plasma free dopamine. Their plasma and urinary free epinephrine responses were less (P < 0.05) than the borderline increases in control subjects. Compared with control subjects, they significantly increased plasma 3, 4-dihydroxyphenylalanine sulfate (P < 0.05), epinephrine sulfate (P < 0.05), and the dopamine sulfate-to-free dopamine ratio (P < 0.02). Postprotein natriuresis is thus associated with nutritional priming-induced plasma but not urinary free dopamine increase. Hypertensive subjects have attenuated natriuretic and plasma free dopamine responses and less free epinephrine increase. This may partly result from higher circulating 3,4-dihydroxyphenylalanine, dopamine, and epinephrine sulfoconjugates leaving fewer free amines for biological actions.

Reduced Urinary Excretion of Dopamine and Metabolites in Chronic Renal Parenchymal Disease

Background: Chronic renal parenchymal diseases are accompanied by a progressive loss of tubular units endowed with the ability to synthesise dopamine from L-3,4-dihydroxyphenylalanine (L-DOPA), and preliminary evidence has suggested that the urinary excretion of free dopamine may be reduced in these disorders. However, it is well recognised now that under in vitro conditions, dopamine newly synthesised in tubular epithelial cells undergoes extensive deamination to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO); a small amount of the amine is converted to homovanillic acid by both MAO and catechol-O-methyltransferase (COMT) and a minor amount is methylated to 3-methoxytyramine. Aims: The present study aimed at examining the relationship between renal function and daily urinary levels of L-DOPA, free dopamine and its main metabolites, DOPAC and homovanillic acid (HVA) in patients (n = 28) with chronic renal parenchymal disease, in conditions of controlled sodium, potassium and phosphate intake. The levels of 5-hydroxyindolacetic acid (5-HIAA) were also evaluated in the same cohort of patients. Results: The patients were divided in two groups according to creatinine clearance (group 1, 39±6 ml/min/1.73 m², n = 14; group 2, 139±6 ml/min/1.73 m², n = 14). In patients of group 1, the urinary levels of L-DOPA, dopamine and DOPAC (in nmol/24 h) were significantly lower (60% reduction) than in patients of group 2 (L-DOPA, 134±36 vs. 308±51; dopamine, 759± 175 vs. 1,936± 117; DOPAC 2,595±340 vs. 7,938±833). Also, the urinary excretion of HVA in patients group 1 was significantly lower (40% reduction) than in patients of group 2 (17,434±2,455 vs. 27,179±2,271 nmol/24 h). By contrast, no significant difference was observed in daily urinary excretion of 5-HIAA between the two groups of patients (group 1, 27,280±3,721 nmol/day; group 2, 28,851±2,854 nmol/day). A positive linear relationship was found in these 28 patients between the creatinine clearance and the daily urinary excretion of L-DOPA (r = 0.64, p < 0.001), free dopamine (r = 0.83; p < 0.0001), DOPAC (r = 0.86; p < 0.0001) and HVA (r = 0.65; p < 0.002), but not with that of 5-HIAA (r = 0.14; ns). The U_{dopamine/L-DOPA} and U_{DOPAC/dopamine} ratios were found to be similar in both groups of patients, whereas the U_HVA/DOPAC ratios in patients of group 1 were found greater than in group 2 (p < 0.05). Conclusion: Patients suffering from chronic parenchymal disease with a compromised renal function present with a reduced activity of their renal dopaminergic system which correlates well with the degree of deterioration of renal function. The reduced urinary dopamine output in renal insufficiency is not attributable to enhanced metabolism of renal dopamine. We suggest that the urinary levels of DOPAC may represent a useful parameter for the assessment of renal dopamine synthesis.

Assessment of renal dopaminergic system activity during the recovery of renal function in human kidney transplant recipients.

The urinary excretion of free dopamine has been used as an index of the renal synthesis of amine. However, it is now well recognized that in the kidney, newly-formed dopamine is significantly inactivated through deamination to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). The aim of the present study was to assess the renal dopaminergic system activity during the recovery of renal function in kidney transplant recipients and to assess which parameters are appropriate for the evaluation of renal amine synthesis under these conditions. Twenty-four-hour urinary excretion of L-DOPA, dopamine and its metabolites (DOPAC; 3-MT; HVA) were continuously monitored in 19 renal transplant recipients from the first day of surgery until the twelfth day post-transplantation. In 11 patients (Group 1), renal function consistently recovered throughout the study (plasma creatinine levels decreased from 6.2 +/- 0.4 to 2.1 +/- 0.1 mg/dl). Eight patients presented with acute tubular necrosis (Group 2) and minimal renal function was maintained until the twelfth post-operative day. The urinary excretion of L-DOPA did not differ throughout the study between the two groups of patients. In contrast, the 24-h urinary levels of dopamine, DOPAC and HVA were significantly higher throughout the study in patients of Group 1: dopamine (Group 1, 179 +/- 26 to 422 +/- 51 nmol/24 h; Group 2, 25 +/- 3 to 57 +/- 13 nmol/ 24 h), DOPAC (Group 1, 698 +/- 57 to 3487 +/- 414 nmol/ 24 h; Group 2, 158 +/- 22 to 1014 +/- 193 nmol/24 h) and HVA (Group 1, 13,058 +/- 1199 to 20,387 +/- 1559 nmol/ 24 h; Group 2, 4140 +/- 848 to 15,219 +/- 1037 nmol/24 h). The recovery of renal function in renal transplant recipients is accompanied by an enhanced ability to synthesize dopamine and inactivate it to DOPAC and HVA. It is suggested that the urinary levels of DOPAC may be a useful parameter for the assessment of dopamine formation in renal tissues.

ROLE OF RENAL DOPAMINERGIC ACTIVITY ON RENAL SODIUM‐WATER METABOLISM IN CONGESTIVE HEART FAILURE

1. The role of the renal dopaminergic system in water-sodium metabolism in heart failure remains unclear. 2. In this study, the urinary free dopamine excretion (uDA), delivery of L-dopa to renal proximal tubules (plasma L-dopa x creatinine clearance (Ccr)), and the production of dopamine in the kidney [uDA/(plasma L-dopa x Ccr)] were investigated in patients with congestive heart failure (n = 30) and in normal controls (n = 12). In both groups, endogenous Ccr, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline concentration (pNA) and plasma L-dopa concentration were also estimated. 3. uDA, plasma L-dopa, delivery of L-dopa and dopamine production in the kidney showed successively lower values in congestive heart failure with progression in NYHA functional class. 4. UNaV (r = 0.458, P < 0.05) and Ccr (r = 0.539, P < 0.01) positively correlated with uDA. Linear correlations were found between left ventricular ejection fraction and uDA (r = 0.574, P < 0.01), pNA (r = -0.495, P < 0.01) or plasma L-dopa (r = 0.423, P < 0.05). 5. From these findings, it was suggested that (i) uDA was clearly suppressed in patients with CHF, and (ii) the possible mechanisms of its suppression might be due to decrease of delivery of L-dopa into the proximal tubules and suppressed production of dopamine from L-dopa in the kidney.

The role of renal dopaminergic activity in the pathophysiology of essential hypertension.

Although the pathogenesis of essential hypertension still remains unclear, it is now generally accepted that the kidney is deeply involved in the pathophysiology of this disease. This paper therefore, reviews current knowledge of the role of renal dopaminergic activity in essential hypertension. This is believed to be one of the most important renal diuretic and depressor systems. Suppression of urinary excretion of free dopamine (DA) is observed in essential hypertensives, particularly in those with low plasma renin activity (LRH) who demonstrate body fluid volume expansion. An increased natriuretic response to exogeneously administered DA is found, particularly in LRH, and suppressed biosynthesis of DA from L-dopa in the kidney has been suggested. Furthermore, this suppression of renal dopaminergic activity was also observed in young normotensive subjects with an apparent family history of hypertension before any evidence of hypertension emerged. From these findings, it is concluded that the decrease in renal dopaminergic activity is involved, at least in part, not only in the pathophysiology of essential hypertension, but also in the pathogenesis of this disease.

The pathophysiological role of renal dopamine and kallikrein in deoxycorticosterone acetate (DOCA)-salt treated rats.

To elucidate the pathophysiological role of the renal dopamine (DA) and kallikrein-kinin systems in volume dependent hypertension under excess mineralocorticoid, the urinary excretions of DA and kallikrein (KAL) were investigated in DOCA-salt treated rats (5 week-old Sprague-Dawley rats, DOCA 100mg pellet, s.c., 1% saline ingestion for 4 weeks, n = 7) for comparison with those of control rats (vehicle, 1% saline ingestion for 4 weeks, n = 10). In vehicle, systolic blood pressure (SBP), urinary excretion of free DA (UDA) and kallikrein (UKAL) did not change through the study. In DOCA treated rats, marked natriuresis was observed with sodium load. SBP and UKAL significantly increased at the 4th week and at the 2nd week, respectively. UDA increased significantly to the peak level at the 1st week, and then decreased gradually. At the 4th week, UDA was significantly lower in DOCA-treated rats than that of vehicle rats. A significant inverse correlation was found between UDA and SBP, and UKAL correlated positively with SBP and urinary excretion of sodium and negatively with UDA in DOCA treated rats. These results suggest that the augmentation of renal dopaminergic activity which may in part cause sodium escape appears at the early stage of DOCA-salt treatment, but this augmentation is subsequently blunted; volume and sodium retention may be associated with the blood pressure elevation at the late stage of DOCA-salt treatment, and that the augmentation of renal kallikrein-kinin system may be a compensatory response to sodium and volume retention in DOCA-salt treated rats.

Urinary Excretion of Free Dopamine and Digoxinlike Substances Correlates with Endogenous Secretion of Insulin in Normotensive Adults, but Not in Hypertensive Subjects

We investigated whether urinary excretion of free dopamine is related with the humoral factors which affect Na+, K+ ATPase activity in the kidneys. Subjects were 51 adults admitted in a hospital without renal insufficiency: they were divided into normotensive (n = 36, 60 +/- 3 years old, 122 +/- 3/73 +/- 2 mmHg) and hypertensive groups (n = 15, 65 +/- 5 years old, 157 +/- 6/91 +/- 2 mmHg). Urinary excretion of free dopamine was significantly and positively correlated with urinary excretion of C-peptide immunoreactivity of insulin (CPR) (r = 0.451, p = 0.014) in normotensive subjects, but not in hypertensive subjects (r = 0.155, p = 0.668). Urinary excretion of endogenous digoxinlike substances (EDLS) was also significantly and positively correlated with urinary CPR (r = 0.500, p = 0.006) in normotensive subjects, but not in hypertensive subjects (r = 0.275, p = 0.363). In normotensive subjects, urinary excretion of free dopamine and EDLS may be regulated at least in part by insulin secreted endogenously. In hypertensive subjects, however, this regulatory mechanism of the diuretic factors, such as insulin, EDLS and dopamine, is thought to be deranged, which might result in decompensation of a diuretic and antidiuretic balance leading to blood pressure elevation.

Diagnostic significance of dopamine estimation using plasma and urine in patients with adrenal and renal insufficiency, renal transplantation and hypertension.

Although free and conjugated dopamine (DA) constitute most of the plasma and urine catecholamine pool, the diagnostic significance of DA estimation for the evaluation of illness is not clear. We evaluated the clinical utility of DA estimation by measuring free and conjugated DA in patients with various illness. Patients with adrenal insufficiency did not show decreases in DA concentrations but did demonstrate reductions in free and conjugated plasma adrenaline (Ad). Patients with established stage of essential hypertension exhibited decreased plasma concentrations of free and conjugated DA, although they were hyperadrenergic. In patients with chronic renal insufficiency and failure, the free DA concentration in the urine decreased depending on the severity of renal impairment. Conversely, plasma concentrations of conjugated DA are higher in patients with chronic renal failure than in normal subjects. The high plasma concentrations of conjugated DA decreased dramatically following hemodialysis and renal transplantation. Urinary free DA excretion increased markedly following renal transplantation. In conclusion, the estimation of the free and conjugated DA in plasma and urine is clinically useful for the diagnosis of adrenal insufficiency, essential hypertension, and renal insufficiency and failure. It also can be used to monitor the effectiveness of hemodialysis and renal transplantation.

Augmentation of the renal tubular dopaminergic activity by oral calcium supplementation in patients with essential hypertension.

We studied the effect of oral calcium supplementation on renal tubular dopaminergic activity in patients with mild to moderate essential hypertension. Fifteen patients aged 45 to 68 years (nine men and six women, mean age 59 +/- 7 [SD]) participated in the study. We orally administered calcium (1.0 g per day for 1 week) during hospitalization. The change in 24-h blood pressure (BP), measured by ambulatory BP monitoring, and excretions of electrolytes and catecholamines were investigated before and after 1 week of oral calcium supplementation. The mean values of 24-h systolic and diastolic BP showed no significant changes by calcium loading. Daily urinary excretion of free dopamine, sodium clearance (CNa), fractional excretion of sodium (FENa), and urinary volume were significantly increased by oral calcium supplementation. Urinary excretions of epinephrine and norepinephrine and creatinine clearance showed no significant changes by oral calcium treatment. CNa and FENa showed significant correlations with urinary excretion of free dopamine. These results suggest that oral calcium supplementation induces natriuresis partly through augmentation of renal tubular dopaminergic activity.

Catecholamines and phosphate excretion by the remnant kidney

The remnant kidney (RK) exhibits an enhanced fractional excretion of phosphate (FEPi) even in the absence of parathyroid hormone (PTH). Thus, factors other than PTH contribute to this adaptive phosphaturia. Dopamine (DA) infusion is phosphaturic, whereas stimulation of adrenoreceptors is antiphosphaturic. Therefore, the hypothesis that alterations in catecholamines by the RK may be associated with the phosphaturia exhibited by this model was tested. Male Sprague-Dawley rats were subjected to right nephrectomy and surgical ablation of the left renal poles. Four weeks later rats with a RK (N = 10) and control rats with intact kidneys (N = 9) were anesthetized and thyroparathyroidectomized (TPTX). Two hours after TPTX, urine samples were collected for measurements of urinary free DA excretion. Subsequently, 3% inulin in saline was infused for one hour and a 30 minute clearance was taken. The kidneys were then removed and frozen for determination of tissue norepinephrine (NE) and DA concentrations. Glomerular filtration rate was significantly lower in rats with a RK than in controls (0.57 +/- 0.07 vs. 0.83 +/- 0.08 ml/min/g kidney wt), whereas fractional excretion of phosphate (FEPi) was significantly higher (29.4 +/- 4.7 vs. 8.3 +/- 3.4%). Tissue NE concentration was significantly lower in the RK than in the control intact kidney (85.10 +/- 4.95 vs. 129.60 +/- 7.20 ng/g), whereas urinary DA excretion per nephron was significantly higher in the RK (0.12 +/- 0.02 vs. 0.04 +/- 0.006 pg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal Sodium Handling and Renal Dopaminergic Activity in Overweight Normotensive Subjects

Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT.

Suppressed dopaminergic activity and water‐sodium handling in the kidneys at the prehypertensive stage of essential hypertension

1. In this study, the question of whether the suppression of the renal dopaminergic system is primary or not was investigated. 2. Renal dopaminergic activity was compared between young healthy normotensive subjects without a family history of hypertension (FH(-] and those with a family history of hypertension (FH(+]. 3. A significant decrease in urinary free dopamine excretion was noted, and the responses of urine volume, urinary sodium excretion, and fractional excretion of sodium to infused dopamine were significantly augmented in FH(+). In addition, a normal level of l-dopa delivery at the renal proximal tubules and a significant reduction in the conversion of l-dopa to dopamine in the kidney were found in FH(+). 4. These findings suggest that renal dopaminergic activity is already suppressed at the prehypertensive stage, and that the reduction in the conversion of l-dopa to dopamine in the proximal tubules may contribute to the attenuation of renal dopaminergic activity in FH(+).

Dopamine in Chronic Renal Failure

In patients with renal disease a reduced renal vasodilatory but conserved natriuretic response to dopamine is observed. An inverse relationship exists between baseline renal function and the dopamine-induced changes in effective renal plasma flow and glomerular filtration rate over a wide range of dopamine doses. The renal hemodynamic response to dopamine is also impaired in kidney donors. In studies with dopamine antagonists and in measurements of urinary free dopamine excretion no evidence was found for increased endogenous renal dopamine generation in these patients. The response of effective renal plasma flow and filtration fraction to fenoldopam was also impaired. However, the fractional sodium excretion in patients with renal disease was not impaired in both short-term and long-term studies. Perhaps this conserved natriuretic effect is of clinical value in these patients.

腎臓内で誘導されたＤｏｐａｍｉｎｅとＮａ利尿作用の関係について

This study was undertaken to elucidate the relationship between natriuresis and renally formed dopamine in pentobarbital-anesthetized rats that were loaded with 0.9% NaCl. Infusion of dopamine resulted in marked increases in urinary free dopamine excretion, plasma free dopamine concentration, urine volume and urinary sodium excretion. Infusion of carbidopa markedly decreased urinary free dopamine excretion, but did not affect urine volume and urinary sodium excretion. Infusion of L-dopa markedly increased urinary free dopamine excretion and plasma free dopamine concentration, but did not affect urine volume and urinary sodium excretion. When carbidopa was infused with L-dopa or dopamine, carbidopa significantly inhibited the increase in urinary and plasma free dopamine induced by L-dopa, but did not inhibit the increases in urinary and plasma free dopamine, urinary sodium excretion and urine volume induced by dopamine. These data indicated that there is no correlation between renally formed dopamine and natriuresis, and furthermore suggested that renally formed dopamine is not essential for natriuresis.

Frusemide, ACE inhibition, renal dopamine and prostaglandins: acute interactions in normal man.

1. The acute effects of intravenous frusemide (30 mg) on prostaglandin dependent renal haemodynamics, urinary prostaglandin excretion, urinary dopamine excretion and electrolyte excretion were studied in six salt replete healthy volunteers with and without pretreatment with the angiotensin converting enzyme (ACE) inhibitor, ramipril (5 mg) and compared with the effects of ramipril alone in order to clarify the role of the renin-angiotensin system in these responses. 2. Frusemide increased natriuresis (UNaV), kaliuresis (UKV), inulin clearance and plasma renin activity (PRA) and ramipril pretreatment significantly enhanced these effects suggesting that the acute generation of angiotensin II (AII) may attenuate these actions of intravenous frusemide. 3. Frusemide increased para-aminohippurate (PAH) clearance, osmolar clearance and urine flow but did not change filtration fraction or urinary kallikrein excretion. Pretreatment with ramipril did not affect these responses. 4. Frusemide increased the excretion of urinary PGE2 and 6-keto-PGF1 alpha. Ramipril pretreatment did not suppress this rise in prostaglandin excretion. Since the frusemide induced prostaglandin dependent renal haemodynamic changes were also not suppressed with ACE inhibition, this suggests that in salt-replete volunteers AII does not significantly modulate renal prostaglandin production after frusemide. 5. Urinary free dopamine excretion increased with frusemide alone. With ramipril pretreatment this rise showed a tendency to increase. AII may therefore inhibit the rise in urinary dopamine excretion after frusemide. However this requires further study.

The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with mean arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients than in normal weight patients with EHT. Hypotensive effect of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight patients with EHT than in normal weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal weight patients with EHT, whereas the relation between the UDA and the BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

Differential effect of guanethidine on dopamine and norepinephrine pools in urine, heart and superior cervical ganglion in the rat

The time-related changes of dopamine (DA) and norepinephrine (NE) pools were investigated in heart, superior cervical ganglion (SCG) and urine in rats treated chronically with guanethidine (50 mg/kg i.p. five days each week). The efficiency of sympathectomy was assessed by the great loss of NE in heart and superior cervical ganglion (SCG) (-96% and -76% respectively of control values on day 18) together with the ready reduction of NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine. The pattern of changes was quite different for DA, which was less readily affected and at a lesser extent than NE in heart and SCG thus suggesting the presence of norepinephrine-independent DA stores. Similarly the urinary excretion of free DA, free 3,4-dihydroxyphenylacetic acid (DOPAC) and free homovanillic acid (HVA) was slightly decreased only from the 9th day, whereas urinary conjugated DA remained unaltered. These results indicate that the greatest portion of urine free and conjugated DA, free DOPAC and free HVA derives from peripheral pools located outside noradrenergic neurons. Alternatively, the time-course of DA sensitivity to guanethidine suggests that a portion of urine DA may originate from DA stored independently from NE in noradrenergic neurons.