Dopamine Excretion Research Articles

Role of intrarenal dopamine on renal phosphate regulation

Dopamine excretion primarily reflects the tubular synthesis of dopamine. Renal dopamine synthesis occurs primarily in the proximal convoluted and straight tubules. Recent studies suggest that increased phosphate intake increases tubular dopamine synthesis. The infusion of dopamine is phosphaturic and enhances the phosphaturic effect of PTH in diverse conditions of phosphate conservation such as phosphate deprivation or acute respiratory alkalosis. Exogenous dopamine specifically inhibits phosphate transport as illustrated by studies of isolated renal brush border membranes. Inhibition of endogenous dopamine synthesis in normal rats with carbidopa has been demonstrated to increase phosphate reabsorption. Dopamine has been suggested to modulate the effect of atrial natriuretic peptide on phosphate excretion in normal rats and in rats with a remnant kidney. The enhanced phosphate excretion in rats with a remnant kidney is associated with increased dopamine synthesis per nephron. Studies performed in the opossum kidney cells which are analogous to proximal tubule cells indicate that these cells synthesize dopamine, increase cAMP levels and decrease phosphate transport by the same cells suggesting an autocrine/paracrine role for dopamine on phosphate transport by proximal tubules.

The effect of salt loading on the urinary excretion of dopamine and sodium transport inhibitor in the rat.

1. The temporal relationship between the excretion of dopamine and sodium transport inhibitor (STI) during salt loading was examined in the rat. 2. Urine samples were collected before and during salt loading (given as 18 g/l NaCl solution to replace drinking water) for the measurement of sodium, creatinine, dopamine and STI in 6 female rats. Dopamine was measured by HPLC and STI was extracted and measured by its ability to inhibit purified Na+, K(+)-ATPase enzyme. 3. Urinary sodium and STI (expressed in relation to creatinine) on day 1 of salt loading were 4.6 and 4.2 times respectively of the control values. Urinary excretion of dopamine did not increase significantly until day 2 when it was 21% higher. 4. The excretion of STI paralleled that of sodium excretion whereas the excretion of dopamine lagged behind. 5. We conclude that salt loading increases STI and dopamine and that the increase in STI precedes that of dopamine.

Lack of renal dopamine production during acute volume expansion in Dahl salt-sensitive rats.

Endogenous kidney dopamine (DA) is reported to contribute to the natriuretic response to acute volume expansion (VE). Several studies suggest that a defect in renal DA-ergic system may play a role in genetic hypertension in humans and rats. The present study was performed to determine the role of renal DA and tubular DA-1 receptors in the natriuretic response to VE in age-matched inbred Dahl salt sensitive (SS/Jr) and salt resistant (SR/Jr) rats of 9-11 weeks of age. In pentobarbital anesthetized rats, VE was carried out by intravenous infusion of isotonic sodium chloride (5% body weight) over a period of 60 min. This maneuver evoked marked increases in urine output and urinary sodium excretion in both SR/Jr and SS/Jr species. However, the natriuretic and diuretic response to VE was significantly reduced in SS/Jr as compared to SR/Jr rats. It was also observed that the urinary excretion of DA was significantly increased during VE only in SR/Jr, but not in SS/Jr rats. In separate group of animals, infusion of DA (1 microgram/kg/min) produced similar increases in urine output and urinary sodium excretion without causing any alterations in blood pressure or heart rate in either SS/Jr or SR/Jr rats. These results suggest that SS/Jr rats are not able to eliminate an acute increase in sodium load as efficiently as SR/Jr, which may be partly due to an impaired endogenous kidney DA production.

Excretion of free catecholamines by children.

Excretion of free noradrenaline, adrenaline and dopamine were studied in random urine samples from 221 children (123 boys and 98 girls). The group was subdivided according to age, from birth to 12 years. The catecholamines were analysed by liquid chromatography with electrochemical detector using a 5 microns C-18 Novapack column at 32 degrees C. The values were expressed per kilogram of creatinine. A statistical analysis (non-paired t-test) was carried out in order to define the different reference groups. Children under 2 years were found to have higher noradrenaline excretion than other ages; children under 4 years had higher adrenaline excretion than other ages. Children under 3 years had the highest dopamine excretion, followed by children between 3-6 years, while children from 7 to 12 had the lowest excretion. Appropriate reference intervals were determined from the results.

The Bergen Blood Pressure Study: inappropriately low levels of circulating atrial natriuretic peptide in offspring of hypertensive families.

Plasma atrial natriuretic peptide (ANP), plasma and 24-h urine catecholamines, plasma renin activity (PRA), and serum aldosterone were studied in offspring of hypertensive and normotensive families [n = 82; age 37 +/- 7 years (mean +/- SD)]. Despite higher age, higher blood pressure, and higher urine excretion of catecholamines--all of which are factors associated with increased ANP levels--the mean basal plasma ANP concentration tended to be lower in offspring of hypertensive than normotensive families. The same pattern was found in all age-tertiles, and the between-group difference was statistically significant in subjects aged 34-39 years (p < 0.01). Also, the family history of hypertension was associated with low ANP levels after covariate adjustment (p < 0.05). The 24-h urine excretion of epinephrine and norepinephrine tended to be higher in offspring of hypertensive than normotensive families while the morning venous plasma levels were similar. The ratio between venous plasma ANP and norepinephrine was lower in offspring of hypertensive than normotensive families (p < 0.05). PRA, serum aldosterone level, and 24-h urine excretion of dopamine did not differ significantly between groups. Inappropriately low basal plasma ANP concentrations and low plasma ANP/norepinephrine ratios may be related to the development of essential hypertension in offspring of hypertensive families.

Insulin causes renal vasodilatation independently of renal prostaglandins in healthy humans

The effect of physiological hyperinsulinaemia on renal haemodynamics and renal sodium handling was studied in nine healthy males on two separate study occasions with and without indomethacin pretreatment, using the euglycaemic insulin clamp technique. Renal haemodynamics and segmental tubular sodium handling were evaluated by determining the inulin, PAH, sodium and lithium clearances. Changes in urinary dopamine excretion were also studied. Insulin infusion caused similar increases in renal plasma flow with as well as without indomethacin pretreatment, but no change in glomerular filtration rate in both experimental settings. Following indomethacin pretreatment, the basal sodium clearance decreased from 1.6 +/- 0.2 to 0.8 +/- 0.2 ml/min and the basal urinary dopamine excretion decreased from 107 +/- 8 to 86 +/- 6 nmol/h. In conclusion, the present study demonstrates a direct renal vasodilatory effect of insulin in healthy subjects that does not seem to be dependent on renal prostaglandins. Moreover, under the present experimental circumstances indomethacin reduced the basal urinary dopamine output, which could reflect a reduction in the filtered load of sodium following indomethacin pretreatment.

Increased Urinary Dopamine Excretion in Young Patients with Essential Hypertension

The evidence that some older patients with essential hypertension have low urinary dopamine excretion has brought into question the levels of urinary dopamine and plasma dopa, the major source of urinary dopamine, in young patients with essential hypertension. Twenty-four-hour urine sodium, creatinine, dopamine and noradrenaline and plasma dopa were evaluated in 48 patients with essential hypertension aged 18 to 27 years and 25 normotensive subjects. In comparison with age-matched normotensive subjects, the hypertensive patients had higher urinary dopamine (1920 +/- 80 vs 1520 +/- 130 nmol/day, p < 0.01) and noradrenaline (216 +/- 11 vs 179 +/- 12 nmol/day, p < 0.05) excretion. There was a significant correlation between urinary dopamine and noradrenaline excretion. There was no difference in plasma dopa levels between normotensive and hypertensive subjects. These results suggest that the elevated conversion of dopa to dopamine in the kidney is leading to increased urinary dopamine excretion in young patients with essential hypertension.

Urinary catecholamine excretion and blood serotonin content in patients with the juvenile hypothalamic syndrome

Daily urinary adrenalin, noradrenalin, dopamine excretion and blood levels ol serotonin were measured over the course of the cycle in 8 healthy girls and in 52 patients with the juvenile hypothalamic syndrome in the acute and chronic stages. These parameters were found virtually the same in healthy girls and in those suffering from the hypothalamic syndrome in the course of the cycle or in patients during the acute and chronic stages of the condition. Urinary catecholamine excretion and blood serotonin levels were increased by 1.5-2 times in the acute stage of the syndrome and somewhat reduced in the chronic stage; this appears to be due to reduced activity of the sympathoadrenal system in the course of disease progress.

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.

Effect of dietary protein on the renal response to fenoldopam in diabetic rats

The effect of the dopamine D 1 receptor agonist, fenoldopam, was studied in streptozotocin-induced diabetic rats treated with insulin to maintain a moderate hyperglycemia and fed a low, normal or high protein diet. Fenoldopam at 1 μg/kg per min i.v. resulted in a significant increase in both glomerular filtration rate (GFR) and renal blood flow (RBF) in diabetic rats fed a normal protein diet. In rats fed a low protein diet, fenoldopam failed to alter either parameter, however, there was a very significant increase in both GFR and RBF in diabetic rats fed a high protein diet. Since diabetes is associated with a decrease in both urinary dopamine excretion as well as the hyperemic response to protein ingestion, it is possible that stimulation of dopamine D 1 receptors by fenoldopam restores renal functional reserve in diabetic animals. The observation that the dopamine D 1 receptor antagonist, SCH 23390, at a dose (1 μg/kg per min) that abolished the renal vasolidator effects of fenoldopam, failed to alter renal hemodynamics in diabetic rats suggests that endogenous dopamine has little effect.

Beneficial Acute Effects of Selective Modulation of Renal Dopamine System by γ-L-Glutamyl-L-Dopa in Rabbits with Congestive Heart Failure

gamma-L-Glutamyl-L-dopa (gludopa) is a dopamine (DA) prodrug with a high degree of renal selectivity. We compared the acute renal effects of gludopa in conscious control rabbits (n = 6) and rabbits with doxorubicin-induced congestive heart failure (CHF, n = 5). Normal saline and gludopa 25 and 100 micrograms/kg/min were infused intravenously (i.v.), each for 60 min. One week later, the same protocol was followed except that the DA-1 antagonist SCH 23390 was given i.v. in a dose of 0.3 mg/kg 10 min before gludopa infusion. An additional control group (n = 6) received the DA-1 antagonist alone and saline vehicle infusion throughout the study period. In both control and CHF groups, gludopa elicited significant and similar increases in urine flow (70, 62%), sodium excretion (127, 98%), and renal blood flow (RBF) (33, 27%), and decreased renal vascular resistance (RVR) (-23, -38%). All these changes were abolished by previous DA-1 antagonism with SCH 23390. Blood pressure (BP), heart rate (HR), and hindlimb blood flow (HBF) remained unchanged during gludopa infusion in both groups. In the control group, but not in the CHF group, plasma renin activity (PRA) increased during gludopa infusion; this was not influenced by DA-1 antagonism. In normal rabbits (n = 6), treatment with SCH 23390 alone had no significant effect on renal excretory function or haemodynamics. During gludopa administration, plasma DA concentration was not significantly altered, whereas urine DA excretion and renal DA content were markedly increased. Intrarenal conversion of gludopa to DA was significantly less in CHF rabbits as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

THE DOPAMINE PRODRUG, GLUDOPA, DECREASES BOTH RENAL AND EXTRARENAL NORADRENALINE SPILLOVER IN CONSCIOUS RABBITS

1. Renal and total noradrenaline (NA) spillover rates were examined under control conditions and during graded infusions of gludopa (gamma-L-glutamyl-L-dopa) in conscious rabbits. 2. Gludopa infusion at 25 and 100 micrograms/kg per min did not alter mean arterial pressure (MAP) and heart rate (HR), but had significant dose-related effects on the renal dopamine (DA) system. At the high dose there were pronounced increases in urinary DA excretion (> 6000-fold) and renal DA content (> 100-fold); renal NA content doubled. 3. Renal venous DA increased after gludopa infusion, but arterial plasma DA concentrations were not significantly changed. Mean arterial plasma gludopa and L-dopa concentrations reached 890, 3190 ng/mL and 3, 10 ng/mL at low and high doses, respectively. 4. Gludopa resulted in a pronounced dose-dependent fall in renal NA spillover, which at 100 micrograms/kg per min accounted for almost half of the reduction in overall NA spillover rate. 5. The significant falls in renal and extrarenal NA spillover rate during gludopa infusion are consistent with suppression of renal and overall sympathetic activity. Gludopa-induced inhibition of renal NA spillover is likely to be due to the actions of DA generated in the kidney on presynaptic DA-2 and alpha-2 receptors. A central sympathoinhibitory mechanism may explain the reduced total NA spillover.

Dietary electrolytes and urinary natriuretic factors

We examined the relationship between the excretion of electrolytes (sodium, potassium and calcium), dopamine and digoxin-like immunoreactive substance in 41 young healthy female subjects (age 18–23 years) in order to study the interaction of electrolyte intake on dopamine and digoxin-like immunoreactive substance-factors which have been postulated to have a pathogenic role in hypertension. Sodium excretion was significantly correlated with dopamine excretion ( r = 0.545, P < 0.0005) and digoxin-like immunoreactive substance ( r = 0.359, P < 0.02). There was also a significant correlation between calcium and digoxin-like immunoreactive substance ( r = 0.345, P < 0.03). Stepwise multiple regression analysis further confirmed that sodium is the only contributor to dopamine excretion and calcium is the only contributor to digoxin-like immunoreactive substance ( r 2 = 0.114). We conclude that in young healthy subjects dopamine excretion is determined partly by sodium intake and that the excretion of digoxin-like immuno-reactive substance is independent of sodium intake.

Sleep disorders and anxiety as symptom profiles of sympathoadrenal system hyperactivity in major depression

Recently, it has been reported that major depression is accompanied by an increased sympathoadrenal system (SAS) activity. In order to study the psychopathological correlates of SAS activity in depression, the authors measured the 24 h urinary excretion of catecholamines (CA), i.e., noradrenaline (NE), adrenaline (E), dopamine (DA) and the NE/E metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in 80 unipolar depressed subjects. The excretion of these indices of SAS activity have been studied in relation to the depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Depression Rating Scale (HDRS). There were significant positive correlations between the SCID item sleep disorders and the HDRS item middle insomia, on the one hand, and NE, E and DA excretion, on the other. The MHPG excretion in 24 h urine was significantly and negatively related to somatic anxiety and hypochondriasis. It is suggested that these intertwined relationships between increased CA turnover, sleep discontinuity and anxiety may reflect the occurence of a hyperarousal state in some major depressives that may be regarded as a coping response to various putative noxious stimuli.

Dissociation of catecholamine and corticosterone responses to different types of stress in rats.

To examine hormonal response patterns to various stresses, urinary excretion of catecholamines and corticosterone was measured in spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) under the following conditions: immobilization, restriction to a small space, introduction of new rats, and noise exposure. In WKY rats, immobilization caused a marked increase in urinary corticosterone, adrenaline and noradrenaline and a decrease in dopamine excretion. Restriction to a small space induced a less pronounced but still obvious increase in adrenaline and corticosterone and a decrease in dopamine. When other rats were introduced into the animal room, the senior rats showed an increase in adrenaline alone, while noise exposure produced an increase in corticosterone alone. These findings suggest that while severe stress, such as immobilization, causes marked changes in all 4 hormones, relatively mild stress produces changes in one to three, not all, hormones, and that catecholamine and corticosteroid responses are dissociated in some forms of the mild stress. It is considered that neuroendocrine responses to stress vary according to both the type of stress and its intensity. In SHR rats, the hormone response to severe stress was greater than in WKY rats, and the response was somewhat less than in WKY rats when exposed to mild stress. These findings do not imply that stress-induced hyperactivity of sympathetic adrenomedullary system participates in the development of hypertension in SHR rats.

Urinary dopamine excretion in conscious rats: effect of carbidopa in different states of sodium balance.

Urinary dopamine excretion was studied in seven different groups of rats (n = 6-12) with the following treatment regimens: normal chow and tap water (controls, CON), single administration of furosemide 20 mg/kg i.p. on day 1 and subsequent feeding of low sodium chow (low salt, LS), normal chow and 1% NaCl as drinking water (high salt, HS), normal chow and 1% NaCl plus deoxycorticosterone acetate 1 mg/kg/day i.p. (high salt plus DOCA, HS+DOCA); carbidopa 20 mg/kg/day p.o. (CDP) was administered in animals on normal chow (CON+CDP), in high salt rats (HS+CDP), and in rats on high salt plus DOCA (HS+DOCA+CDP). On day 5, rats were placed in metabolic cages with free access to their respective drinking solution; chow was withheld. Urine was collected for 24 h and analyzed for sodium, creatinine, and dopamine. Urinary dopamine excretion rates did not change in proportion to large differences in sodium excretion in LS, HS, and HS+DOCA animals compared to CON. Only when urinary dopamine excretion of HS rats was compared to the LS group there was a moderate, but significant increase of 27%. In the groups treated with CDP renal dopamine excretion was decreased by approximately 60% in comparison to the groups with the respective treatment condition but without CDP. Urinary sodium output was unchanged by CDP in CON+CDP animals compared to CON. In HS+CDP and HS+DOCA+CDP groups renal sodium excretion was reduced by half compared to the HS and HS+DOCA groups, respectively. However, this effect was accompanied by a similar, approximately 55% reduction of oral volume and sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary dopamine and sodium excretion in spontaneously hypertensive rats.

We measured urinary dopamine in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before (days 0-6) and during high-salt diet, in the absence (days 6-10) and presence (days 10-14) of added L-dopa (2 mg/kg/day by gavage). Urinary excretion of sodium (UNaV) increased 20-fold during intake of chow containing 8% NaCl in both strains. Systolic blood pressure (SBP) of SHR increased slightly (9 +/- 4 mmHg; p < 0.05) on the high-salt diet, whereas SBP did not change in WKY. Urinary dopamine excretion was not different between strains in the basal state, and was as great or greater in SHR than WKY during high-salt intake with and without added L-dopa. SBP was unaffected by L-dopa administration and UNaV did not increase or differ between strains despite higher urinary dopamine excretion in SHR. We conclude that renal dopamine formation in vivo is not diminished in SHR, compared with WKY, on normal or high-salt diets, and that elevation of renal dopamine formation secondary to L-dopa administration is not associated with reductions in SBP or altered UNaV in these rats.

Insulin Levels, Physical Activity, and Urinary Catecholamine Excretion of Obese and Non‐Obese Rhesus Monkeys

The hypothesis that spontaneous obesity in rhesus monkeys is associated with abnormalities in energy expenditure was tested. Obese (n=7) and non-obese (n=5) monkeys were described in terms of body size and composition, food intake, and physical activity. Additionally, the relationships among fasting and stimulated insulin levels in serum, C-peptide levels in serum and urine, and urinary catecholamines were examined. Obese animals had primarily abdominal deposition of excess body fat, as indicated by markedly elevated abdominal circumferences and skin-fold thicknesses. Food intake did not differ between groups. Physical activity was much lower in the obese group. Obese monkeys had markedly higher serum insulin and C-peptide levels in the fasted state and in response to an intravenous glucose challenge. Urinary excretion of C-peptide and catecholamines was measured during successive 2-day periods of ad libitum feeding, food deprivation, and refeeding in order to examine potential differences between groups in sympathoadrenal activity and their relationship to insulin secretion. C-peptide excretion was greater for obese and decreased for both groups during food deprivation. Urinary dopamine (DA), norepinephrine (NE), and epinephrine (E) levels were significantly greater for obese animals in all conditions. DA excretion was lowest during deprivation and E excretion was lowest during refeeding, whereas NE excretion was relatively unaffected by feeding condition. The overall patterns of C-peptide and catecholamine excretion were qualitatively similar for both groups, and there were no reliable differences between obese and non-obese in their responses to the feeding manipulation. The results suggest that hyperinsulinemia associated with obesity in rhesus monkeys is linked to increased catecholamine secretion and a resistance to catecholaminergic action.

Individual differences in sympathetic nervous system responses to white noise stimuli: an investigation by finger plethysmogram

Possible individual variations in the sympathetic nervous system response to sound stimuli were investigated using the auditory evoked plethysmogram response (AEPGR). This study consists of the following 3 experiments; (EXP1) the sound level-response relationships between white noise at 50, 70, and 90 dB (A) and AEPGRmax as defined below, (EXP2) individual variations of AEPGRmax to white noise at 90 dB (A), and (EXP3) the relationship between the AEPGR pattern and the urinary catecholamine (CA) excretion rate during sleep on the preceding night. The subjects were 35 young persons in (EXP1), and 79 young (18-28 yrs. old) and 35 old (60-83 yrs. old) persons in (EXP2) and (EXP3), respectively. The results were: (1) a good sound level-response relationship between the sound levels of 50, 70, and 90 dB (A) and AEPGRmax was obtained on average; (2) an AEPGRmax of more than 100% in response to the 90 dB (A) white noise was found in about 10% of the subjects, whereas it was below 100% in 90% of them. The time prior to the maximum response in the former case varied from 4.6 to 22.2 sec, which was quite a contrast to that of 3.0-9.0 sec in the latter case; (3) The NE (norepinephrine), E (epinephrine) and DA (dopamine) excretion rates were shown to be significantly higher in the former group in (2) than in the other groups, regardless of adjustment for age, blood pressure and/or ECG findings. Thus, it is suggested that the cardiac response to E secreted from the adrenals due to white noise stimuli was predominant in the former group in (2). Therefore, this response pattern was called the AEPGR "beta type", whereas the other group was designated the "alpha type", since its AEPGR appeared to reflect only vasoconstriction. The suggested individual differences in AEPGR associated with increased night-rest catecholamine secretion were also discussed in relation to their possible relevance to chronic stress, neuroticism and other conditions.