Suppression of norepinephrine secretion by dopamine in children with neuroblastoma: evidence for precursor inhibition in catecholamine pathway

To elucidate catecholamine (CA) secretory dynamics in neuroblastoma, urinary excretion of CAs and their metabolites was serially measured in 6 patients aged 3 months to 3 years before and during treatment. After tumor extirpation, increased urinary CAs were promptly normalized; the reduction reflected the amount of CA production from the tumor. Urinary dopamine (DA) showed the most prominent reduction, whereas DA content in the tumor was very small, indicating that the DA produced was immediately released from the tumor and metabolized in extra-tumor tissues. In contrast, patients receiving chemotherapy continued to excrete excess DA and homovanillic acid (HVA), which were increased further at recidivation. One patient showed an inverse correlation between DA and norepinephrine (NE) excretion; a decrease in DA was associated with an increase in NE and plasma DA-beta-hydroxylase (DBH) activity. A similar inverse correlation was also noted between NE and vanillylmandelic acid (VMA) or 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion, while HVA and dihydroxyphenylacetic acid (DOPAC) were positively correlated with DA excretion. Urinary HVA and VMA were lineally correlated but in a patient excreting an enormous amount of DA, urinary VMA was markedly suppressed in terms of HVA excretion. Excessive DA induced an increase in renal water output but did not enhance Na and K excretion. These results indicate that endogenous DA overload in neuroblastoma inhibits NE production by suppressing DBH activity as well as by forming VMA and MHPG. This precursor regulation appears to be the characteristic of the CA metabolic pathway.     

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 cate-cholaminergic action.     

Effect of "no added salt diet" on blood pressure control and 24 hour urinary sodium excretion in mild to moderate hypertension

Background

The incidence of Hypertension as a major cardiovascular threat is increasing. The best known diet for hypertensives is 'no added salt diet'. In this study we evaluated the effect of 'no added salt diet' on a hypertensive population with high dietary sodium intake by measuring 24 hour urinary sodium excretion.

Methods

In this single center randomized study 80 patients (60 cases and 20 controls) not on any drug therapy for hypertension with mild to moderate hypertension were enrolled. 24 hour holter monitoring of BP and 24 hour urinary sodium excretion were measured before and after 6 weeks of 'no added salt diet'.

Results

There was no statistically significant difference between age, weight, sex, Hyperlipidemia, family history of hypertension, mean systolic and diastolic BP during the day and at night and mean urinary sodium excretion in 24 hour urine of case and control groups. Seventy eight percent of all patients had moderate to high salt intake. After 6 week of 'no added salt diet' systolic and diastolic BP significantly decreased during the day (mean decrease: 12.1/6.8 mmhg) and at night (mean decrease: 11.1/5.9 mmhg) which is statistically significant in comparison to control group (P 0.001 and 0.01). Urinary sodium excretion of 24 hour urine decreased by 37.1 meq/d ± 39,67 mg/dl in case group which is statistically significant in comparison to control group (p: 0.001). Only 36% of the patients, after no added salt diet, reached the pretreatment goal of 24 hour urinary sodium excretion of below 100 meq/dl (P:0.001).

Conclusion

Despite modest effect on dietary sodium restriction, no added salt diet significantly decreased systolic and diastolic BP and so it should be advised to every hypertensive patient.

Trial Registration

Clinicaltrial.govnumber NCT00491881     

Plasma catecholamines and urinary excretion of their main metabolites in three models of portal hypertension

We have measured, by a specific radioenzymoassay, the plasma concentration of dopamine (DA) and norepinephrine (NE) and by gas chromatography the urinary excretion of some catecholamine metabolites (HVA, homovanillic acid, DOPAC, dihydroxyphenyl acetic acid; VMA, vanilmandelic acid, and DOPEG, dihydroxyphenyl glycol) in three groups of rats with portal hypertension: cirrhotic rats (CR), rats with progressive portal hypertension (PPH) and rats with progressive hepatic congestion (PHC). The three groups of rats had portal hypertension. PPH and PHC had also intrahepatic hypertension. CR rats showed an increased urinary excretion of NE and DA metabolites with a normal plasma concentration of these catecholamines, suggesting an increased turnover of NE and DA in this experimental model. PPH animals had a high plasma DA concentration with a decreased urinary excretion of catecholamine metabolites. PHC showed high plasma DA and NE levels with normal or increased urinary excretion of its metabolites. These results suggest that an increased neural activity is present in the early stages of experimental cirrhosis in rats and this alteration does not seem directly related to the portal hypertension but perhaps to the intrahepatic hypertension or to the hepatocellular damage.     

Effect of dietary copper deficiency on the distribution of dopamine and norepinephrine in mice and rats

Dietary copper deficiency was produced in Swiss albino mice and Sprague Dawley rats to determine the organ specificity of alterations in norepinephrine (NE) and dopamine (DA) concentrations and the relationship with organ copper levels. A 5-week dietary treatment was used, which started 1 week after birth for mice, initially via dams, and 3 weeks after birth for rats. Mice offspring (6 weeks of age) and rats (8 weeks of age) maintained on a copper-deficient (-Cu) treatment were compared with copper-adequate (+Cu) controls. Compared with +Cu animals, -Cu mice and rats were anemic and had low (<1% of +Cu) ceruloplasmin activities but normal body weights. The -Cu mice had organ copper concentrations ranging between 30% and 65% of +Cu values for eight organs studied, with the thymus being the least depleted. For -Cu rats, the range was 15% to 65%. Significant reductions in NE concentration were observed in the heart, pancreas, and spleen of -Cu mice. Elevated DA levels were observed in all organs except the brain. For -Cu rats, the NE level was lower in the heart and the DA level was higher in both the heart and spleen compared with +Cu rats. Dopamine elevation in the heart and spleen for both -Cu mice and rats was four- and fivefold higher, respectively. Adrenal catecholamine levels were only slightly changed by copper deficiency in mice or rats. Urinary levels of both NE and DA were higher in -Cu rats and mice. Plasma and heart tyrosine levels were not altered in -Cu mice. Elevated DA in -Cu rodents may be due to limiting dopamine-beta-monooxygenase. Higher urinary NE and lower organ NE may be due to a combination of decreased synthesis and enhanced turnover. The magnitude of decreased organ copper was not predictive of altered catecholamine pool size.     

Studies on renal excretion of potassium in the dik-dik antelope

1. In a study on the renal handling of potassium by the dik-dik antelope, plasma and urine samples were analysed for potassium, sodium and creatinine concentrations and osmolality during dehydration and intra-ruminal loading of potassium solutions. 2. The fractional excretion of potassium was 0.64 during the control period and rose up to as high as 2.3 during potassium loading. Urinary osmolality and potassium concentration decreased as the urine volume increased but the total amounts of potassium excreted were independent of urine volume. 3. Potassium loading led to a steady increase in its urinary excretion but a decrease in plasma potassium concentration was observed. This observation casts doubt on the hypothesis that alterations in potassium intake produce parallel alterations in plasma potassium concentration (which supposedly stimulates or depresses potassium excretion) and thereby maintain potassium homeostasis. 4. A possible alternative signal for increased potassium excretion following increased intake is discussed.     

Dopaminergic modulation of salt sensitivity in patients with essential hypertension

The present study was designed to investigate the possible role of dopaminergic mechanisms in contributing to the pathogenesis of hypertension in salt sensitive patients. Eighteen patients with essential hypertension were studied while under a diet ranging from low salt to high salt, which enabled a classification in "salt-sensitive" (SS) and "nonsalt-sensitive" (NSS) groups based on a tentative criteria of a 10% increase of mean blood pressure with high salt diet. The SS patients showed reduced urinary excretion of sodium as compared with that from NSS patients. Urinary norepinephrine excretion in all patients with salt loading was suppressed, but urinary excretion of epinephrine showed a tendency to increase in SS patients after salt loading. Urinary excretion of dopamine increased in NSS patients with salt loading, but did not change in SS patients. To further evaluate the role of dopaminergic mechanisms in salt-sensitive hypertension, metoclopramide, a dopamine antagonist, was injected intravenously to all patients. With salt loading, plasma aldosterone levels increased after injection of metoclopramide in NSS patients, but did not change in SS patients. These results suggest that salt-sensitive hypertension is modulated by dopaminergic activity, which in turn is attenuated in SS patients. Decreased dopaminergic activity induced sodium retention both by a direct effect on the kidney as well as indirectly via relatively increased aldosterone secretion. Both mechanisms would help to increase intravascular volume and blood pressure in salt-sensitive hypertension.     

Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans

The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), urinary excretion of PGE(2) (u-PGE(2)) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE(2) were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism.     

Alterations in Regional Brain Catecholamine Concentrations After Experimental Brain Injury in the Rat

Abstract: Although activation of brain catecholaminergic systems has been implicated in the cerebrovascular and metabolic changes during subarachnoid hemorrhage, cerebral ischemia, cortical ablation, and cortical freeze lesions, little is known of the response of regional brain catecholamine systems to traumatic brain injury. The present study was designed to characterize the temporal changes in concentrations of norepinephrine (NE), dopamine (DA), and epinephrine (E) in discrete brain regions following experimental fluid-percussion traumatic brain injury in rats. Anesthetized rats were subjected to fluid-percussion brain injury of moderate severity (2.2–2.3 atm) and killed at 1 h, 6 h, 24 h, 1 week, and 2 weeks postinjury (n = 6 per timepoint). Control animals (surgery and anesthesia without injury) were killed at identical timepoints (n = 6 per timepoint). Tissue concentrations of NE, DA, and E were evaluated using HPLC. Following brain injury, an acute decrease was observed in DA concentrations in the injured cortex ( p < 0.05) at 1 h postinjury, which persisted up to 2 weeks postinjury. Striatal concentrations of DA were significantly increased ( p < 0.05) only at 6 h postinjury. Hypothalamic concentrations of DA and NE increased significantly beginning at 1 h postinjury ( p < 0.05 and p < 0.05, respectively) and persisted up to 24 h for DA ( p < 0.05) and 1 week ( p < 0.05) for NE. These data suggest that acute alterations occur in regional concentrations of brain catecholamines following brain trauma, which may persist for prolonged periods postinjury.     

Free and conjugated catecholamines and metabolites in cat urine after hypoxia

Catecholamine and metabolite excretion was studied in the cat after 6 h of 7.5% O2 hypoxia. Norepinephrine (NE) release from sympathetic nervous endings was strongly activated, whereas epinephrine (E) excretion was only slightly increased. A noteworthy result was the increase of dopamine (DA) and its metabolites [3-methoxytyramine (MT); 3,4-dihydroxyphenylacetic acid (DOPAC)] in urine samples. This increased release does not seem to originate from the central nervous system, but rather from peripheral dopaminergic structures; available knowledge on peripheral DA suggests that the hypoxia-induced DA release might be partly related to chemosensory or renal function. Indeed, in addition to enhanced DA and NE excretion, we observed an increase in sodium excretion that correlated with both DA and NE. Analysis of free and conjugated urinary metabolites showed that only free NE and both free and conjugated normetanephrine were increased in urine after hypoxic stress. Among DA metabolites, conjugated DOPAC was the main DA metabolite in the basal state and after hypoxia. Both the free and the conjugated forms of DA, MT, and DOPAC were increased by hypoxia.     

Role of transmitters in mediating hypothalamic control of electrolyte excretion.

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.     

Effect of dietary calcium on renal prostaglandins.

The present study was designed to clarify the possible role of renal prostaglandins (PGs) on blood pressure (BP) regulation during calcium (Ca) restriction or supplementation. Twelve normotensive women with a mean age of 21.2 years participated in the study. After 1 week of normal Ca intake (mean +/- SE, 536 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for a further 1 week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. BP, heart rate, and serum total and ionized Ca concentrations were measured at the end of each period. Levels of Ca, sodium, PGE2, 6-keto-PGF1 alpha and thromboxane (TX) B2 excreted into urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in both groups. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. BP was not altered after Ca deprivation or loading. However, urinary PGE2 excretion was significantly augmented from 668.9 +/- 68.1 to 959.7 +/- 183.1 ng/day by Ca loading, whereas Ca deprivation decreased PGE2 excretion (695.4 +/- 108.1 to 513.2 +/- 55.2 ng/day). No changes were observed in 6-keto-PGF1 alpha or TXB2 urinary excretion. These results suggest that renal PGE2 synthesis is stimulated or decreased by 1-week Ca loading or deprivation, indicating a possible antihypertensive role of renal PGE2 during high-Ca intake in hypertensives.     

Sex differences in the urinary catecholamines.

Urinary excretion of dopamine, norepinephrine and epinephrine was measured in a group of adult men and women of comparable age during recumbency and then during stimulation by upright posture. Urinary norepinephrine was found to be significantly higher in women (30.3 +/- 4.4 ng/min/m2 B.S.) than in men (18.3 +/- 2.7 ng/min/m2 B.S.) during recumbency; there was no significant sex difference in dopamine and epinephrine excretion. There was no apparent trend indicating a difference in urinary catecholamine excretion during the follicular or luteal phase of the menstrual cycle. In response to upright posture, there was a significant decrease in the urinary dopamine-norepinephrine ratio in both sexes; the magnitude of the decrease was, however, significantly higher in men (-9.9 +/- 3.0) than in women (-2.05 +/- 0.72). The mechanisms of the sex differences in urinary catecholamine excretion are unknown. Clinical studies involving catecholamines have to take these sex differences into account.     

Effects of atrial natriuretic factor on urinary concentration of catecholamines and renin secretion in dogs

This study evaluated the effects of synthetic atrial natriuretic factor (ANF) on renal hemodynamics, urinary excretion of electrolytes, norepinephrine (NE), and dopamine (DA); and renal production of renin in anesthetized dogs. Following a bolus (1 micrograms/kg body weight) and infusion (0.1 microgram/kg/min) for 30 min, there was significant increase in urine flow (220 +/- 41%), glomerular filtration rate (72 +/- 14%), and urinary sodium excretion (170 +/- 34%). There was a decrease in renin secretory rate and the concentration ratio of urine NE to DA following ANF was decreased (p less than 0.05). These data suggest that ANF decreases renal production of NE and renin.     

Atrial natriuretic peptide--cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man

The present study examines hormonal and renal responses to acute volume expansion in normal man, with particular emphasis on the atrial natriuretic peptide (ANP)--cyclic GMP coupling. Two liters of isotonic saline were infused into eight normotensive male subjects over a 1-h period. Plasma and urinary measurements were made before, during, and up to 300 min after the start of the saline infusion. With the initial increase in urinary sodium excretion there were increases in plasma ANP and plasma cyclic GMP, which reached maximum levels at 15 min after the end of the saline infusion. Urinary cyclic GMP increased gradually during saline infusion up to approximately 60 min after the end of the infusion. Plasma ANP and plasma and urinary cyclic GMP excretion gradually declined thereafter. By contrast, urinary sodium excretion remained elevated up to the end of the observation period. The saline infusion was associated with marked reductions in plasma renin activity and aldosterone, which persisted up to the end of the study. These results suggest a coupling between the increases in plasma ANP, the production of cyclic GMP, and urinary sodium excretion, in particular during the initial renal response to acute volume expansion. However, other mechanisms including the suppression of the renin--angiotensin--aldosterone system may become increasingly important in the later natriuretic response to acute volume expansion.     

Catecholamine and thyroid hormone metabolism in a case of anorexia nervosa

Alterations in catecholamine (CA) and thyroid hormone metabolism were examined in a 12-year-old girl with anorexia nervosa during 3 months of treatment. According to her body weight change, the observation period was divided into 3 stages: initial emaciation (stage 1), stable maintenance of the -30% level of the previous weight (stage 2) and convalescent stage (stage 3). Stage 1 was characterized by relatively high urinary norepinephrine (NE) and epinephrine (E) but low dopamine (DA) excretion, elevated plasma DA-beta-hydroxylase (DBH) activity and reduced serum thyroid hormones, especially the triiodothyronine (T3) level. In stage 2, urinary CAs were markedly suppressed, while serum thyroid hormones gradually increase. In stage 3, a great increase in DA excretion, a fall in plasma DBH activity and normalization of thyroid hormones were observed. In the low T3 state below 60 ng/dl, urinary NE + E/DA ratios were elevated and widely fluctuated (0.58 +/- 0.30, SD), but were gradually decreased and completely stabilized in the normal T3 state (0.07 +/- 0.02, P less than 0.001). These results indicate that (1) although total CA production was depressed in anorexia nervosa, a change from an adrenergic-dominant to a dopaminergic-dominant state occurs in accordance with body weight gain, and (2) this shift in the CA profile is associated with concomitant recovery of reduced thyroid hormone concentrations. Thus, as for the energy expenditure, compensatory changes were observed in CAs and thyroid hormones in relation to caloric restriction.     

The effect of sodium intake on renal prostaglandin production

The effect of chronic alterations in dietary sodium intake on renal arachidonic acid (AA) metabolism was studied in male Wistar rats who were maintained for 14 days on a diet consisting of sodium-deficient food and either deionized water (low salt intake, LSI), 1% saline (normal salt intake, NSI), or 2% saline (high salt intake, HSI). 24 h Urinary Sodium (UNaV) and plasma renin activity (PRA) measurements were shown to validate the dietary protocol. Microsomal preparations from the cortices and medullae were incubated with radiolabeled exogenous AA, and endogenous urinary prostaglandin (PG) levels were assayed by RIA to quantify renal PG synthesis. Cortical PGF2 alpha and PGE2 synthesis was found to be the greatest following LSI. In contrast, medullary PGF2 alpha was shown to be the least following LSI and to increase with increased sodium intake. Likewise, urinary PGF2 alpha levels significantly increased with increasing sodium intake. Changes in urinary PGE2 levels showed the same trend as PGF2 alpha but did not achieve statistical significance. These data show that dietary sodium differentially affects renal cortical and medullary PG synthesis and may reflect physiological differences in the regulation of cyclooxygenase in these zones. These data further suggest that the major source of urinary PGs is the renal medulla since the relationship of urinary levels to sodium intake mimics that described for the synthesis of PGs by the medullary tissue.     

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22-40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60-80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (P(f)) and backward (P(b)) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (P(b)/P(f)) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.     

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.     

Effect of sodium and chloride depletion on urinary prostaglandin F2α excretion in potassium loaded rats

Previous studies have shown that the urinary excretion of prostaglandin (PG) F2 alpha is stimulated by potassium (K) loading. Because changes of sodium chloride (NaCl) intake also affect renal PG production, in this study we investigated the interaction between the effect of K and that of concomitant reduction of Na and Cl intake. The urinary excretion of PGF2 alpha and PGE2 was measured in 12 groups of female rats on normal, high or low K intake. Na and Cl intake were adjusted so that rats had normal intake (controls, C), were selectively Cl depleted (CD), selectively Na depleted (ND) or Na and Cl depleted (NCD). In rats with normal K intake, urinary PGF2 alpha was not modified by changes of Na or Cl intake, whereas PGE2 was increased in by Cl depletion (in both NCD or CD groups). Potassium chloride loading increased urinary PGF2 alpha and selective Na depletion (ND group) induced a further increase. On the other hand, PGF2 alpha was not stimulated when K load was associated with Cl depletion. Urine PGF2 alpha was directly correlated with plasma aldosterone and urinary kallikrein. Urinary PGE2 did not change with K-loading. The results suggest that PGF2 alpha participates in the renal adaptation to KCl-loading but not when K is accompanied by non-Cl anions.