Gastrointestinal osmoreceptors and renal sodium excretion in humans

The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogastric tube as isotonic or hypertonic saline (850 mM). In additional experiments, salt loading was replaced by oral water loading (3.5% of total body water). Plasma sodium concentration increased after hypertonic saline (+3.1 +/- 0.7 mM), decreased after water loading (-3.8 +/- 0.8 mM), and remained unchanged after isotonic saline. Oncotic pressure decreased by 9.4 +/- 1.2, 3.7 +/- 1.2, and 10.7 +/- 1.3%, respectively. Isotonic saline induced an increase in renal sodium excretion (104 +/- 15 to 406 +/- 39 micromol/min) that was larger than seen with hypertonic saline (85 +/- 15 to 325 +/- 39 micromol/min) and water loading (88 +/- 11 to 304 +/- 28 micromol/min). Plasma ANG II decreased to 22 +/- 6, 35 +/- 6, and 47 +/- 5% of baseline after isotonic saline, hypertonic saline, and water loading, respectively. Plasma atrial natriuretic peptide (ANP) concentrations and urinary excretion rates of endothelin-1 were unchanged. In conclusion, stimulation of osmoreceptors by intragastric infusion of hypertonic saline is not an important natriuretic stimulus in sodium-replete subjects. The natriuresis after intragastric salt loading was independent of ANP but can be explained by inhibition of the renin-angiotensin system.     

Urinary N tau-methylimidazole acetic acid excretion in respiratory disease

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.     

18-oxocortisol: effect of dexamethasone, ACTH and sodium restriction

The urinary excretion of 18-oxocortisol in 37 normal subjects consuming a normal sodium diet was 1.2 +/- 0.9(SD) microgram/24 h. Dexamethasone administration to 5 normal individuals suppressed the excretion of 18-oxocortisol from 1.16 +/- 0.5 micrograms/24 h to 0.6 +/- 0.2 micrograms/24 h. While they still received dexamethasone, ACTH administration raised the 18-oxo-cortisol excretion to 3.82 +/- 1.2 micrograms/24 h. Seven normal subjects were placed on a sodium restricted diet, and the urinary excretion of 18-oxocortisol rose from 1.5 +/- 1.21 micrograms/24 h to 8.54 +/- 5.08 micrograms/24 h and aldosterone from 6.6 +/- 2.0 micrograms/24 h to 39.7 +/- 14.6 micrograms/24 h. Two of the seven individuals showed minimal increases in the excretion of 18-oxocortisol, but in all cases aldosterone increased with sodium restriction. The urinary excretion of 18-oxocortisol correlated significantly with the excretion of aldosterone, 18-hydroxycortisol, cortisol, and 19-nordeoxycorticosterone. These studies indicate that 18-oxocortisol secretion is under ACTH regulation, but since sodium restriction also increases the excretion of 18-oxocortisol, the renin-angiotensin system must also participate in its regulation. However, some individuals do not increase their excretion of 18-oxocortisol with sodium restriction, although aldosterone excretion increases as expected, suggesting that additional factors participate in the regulation of 18-oxocortisol production.     

Über die Gewöhnung von Ziegen an eiskaltes Tränkwasser

90 urine samples obtained in three lamb trials and one experiment using adult wethers were analyzed for their contents of orotic acid and creatinine. The average daily excretion of orotic acid accounted for 0.5 mg to 1.5 mg (35 μg to 130 μg/W^0.75) with a high individual variation. Correlation coefficients between orotic acid and other urinary constituents were low indicating an entirely different response to metabolic variations. There was only a weak relationship to live weight, protein retention and rumen fluid traits. Defaunation reduced the orotic acid excretion (significant in the adult wethers) whereas the addition of rumen‐protected lysine as well as the use of different dietary carbohydrate sources were without effect. The urinary excretion of creatinine increased with live weight and age from 0.4 g/d in the 20 kg lambs to 1.7 g/d in the adult 53 kg wethers. The correlations with live weight were close whereas the apparently negative correlation with protein retention was not real as could be evaluated by calculation of the partial correlations. There was a close correlation of creatinine with total N, urea and allantoin. Neither defaunation nor rumen‐protected lysine and the kind of carbohydrate source had significant effects on creatinine. The use of orotic acid and creatinine as indicators of metabolic disorders were discussed. Easy application in practical diagnosis without quantitative urine collection might be possible by the determination of orotic acid in the milk of cows and of the creatinine/N ratio in urine.     

Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hydroxycobalamin[c-lactam] on propionate and carnitine metabolism in the rat.

The administration in vivo of the cobalamin analogue hydroxycobalamin[c-lactam] inhibits hepatic L-methylmalonyl-CoA mutase activity. The current studies characterize in vivo and in vitro the hydroxycobalamin[c-lactam]-treated rat as a model of disordered propionate and methylmalonic acid metabolism. Treatment of rats with hydroxycobalamin[c-lactam] (2 micrograms/h by osmotic minipump) increased urinary methylmalonic acid excretion from 0.55 mumol/day to 390 mumol/day after 2 weeks. Hydroxycobalamin[c-lactam] treatment was associated with increased urinary propionylcarnitine excretion and increased short-chain acylcarnitine concentrations in plasma and liver. Hepatocytes isolated from cobalamin-analogue-treated rats metabolized propionate (1.0 mM) to CO2 and glucose at rates which were only 18% and 1% respectively of those observed in hepatocytes from control (saline-treated) rats. In contrast, rates of pyruvate and palmitate oxidation were higher than control in hepatocytes from the hydroxycobalamin[c-lactam]-treated rats. In hepatocytes from hydroxycobalamin[c-lactam]-treated rats, propionylcarnitine was the dominant product generated from propionate when carnitine (10 mM) was present. The addition of carnitine thus resulted in a 4-fold increase in total propionate utilization under these conditions. Hepatocytes from hydroxycobalamin[c-lactam]-treated rats were more sensitive than control hepatocytes to inhibition of palmitate oxidation by propionate. This inhibition of palmitate oxidation was partially reversed by addition of carnitine. Thus hydroxycobalamin[c-lactam] treatment in vivo rapidly causes a severe defect in propionate metabolism. The consequences of this metabolic defect in vivo and in vitro are those predicted on the basis of propionyl-CoA and methylmalonyl-CoA accumulation. The cobalamin-analogue-treated rat provides a useful model for studying metabolism under conditions of a metabolic defect causing acyl-CoA accretion.     

Estimation by gas chromatography-mass spectrometry with selected ion monitoring of urinary excretion rates of 3 alpha-androstanediol during/after i.v. administration of 13C-labelled testosterone in man

To study in vivo the conversion of testosterone (T) into its metabolites, dihydro-testosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta diol (3 alpha-Diol) the urinary excretion rates of these steroids were determined by mass spectrometry in 6 healthy men during/after the i.v. infusion (t = 4 h) of 20 mg [13C]testosterone. In addition, plasma concentrations of T, DHT and 3 alpha-Diol were determined by radioimmunoassay. During steady state conditions at the end of the 4-h infusion of [13C]T the increase in the plasma concentrations of T from, basal, 405 +/- 140 ng/dl to 4205 +/- 804 ng/dl was paralleled by an increase in the plasma concentrations of DHT to 106.4 +/- 62.5 ng/dl) (basal: 30.8 +/- 21.8 ng/dl), and of 3 alpha-Diol to 32.2 +/- 12.5 ng/dl (basal: 12.5 +/- 13.9 ng/dl). Plasma concentrations of T, DHT and 3 alpha-Diol then returned to basal concentrations within 24 hours. Using mass-spectrometry we found a cumulative renal excretion of 13C-labelled T of 15.6 +/- 9.6 micrograms/24 h, equivalent to 0.08 +/- 0.05% of the infused amount (20 mg) of [13C]T. Whereas urinary excretion of [13C]DHT was below the level of detection by mass-spectrometry the cumulative excretion of [13C]3 alpha-Diol was 67.7 +/- 19.9 micrograms/24 hours which is equivalent to 0.3 +/- 0.1% of the infused dose of 13C-labelled testosterone. These data suggest that the determination of urinary 3 alpha-Diol by mass-spectrometry during/after the infusion of stable-labelled testosterone represents an alternative to the use of radioactive label for turnover studies.     

The influence of endogenous mineralocorticoids on the composition of fetal urine

Experiments were carried out in 10 chronically catheterised fetal sheep aged 121-128 days. In 3 animals infusion of aldosterone (5 micrograms/h) caused a fall in fetal urinary Na/K ratio; an effect that was reversed by spironolactone 2.5 mg/kg followed by an infusion of 100 micrograms/h per kg. In 9 fetal sheep which had no previous treatment the same doses of spironolactone had no effect on fractional sodium excretion although the fractional excretion of potassium decreased (P less than 0.05) and the urinary sodium potassium (Na/K) ratio rose (P less than 0.05). Amiloride had a variable effect on sodium excretion but the fractional excretion of potassium decreased markedly (P less than 0.05). Thus in chronically catheterised fetal sheep, endogenous mineralocorticoid activity altered urinary potassium excretion and the urinary Na/K ratio. However this activity was low, as distal blockade with amiloride further decreased the fractional excretion of potassium and increased the urinary Na/K ratio.     

Contribution of propionate to glucose synthesis in sheep

1. The production rate of propionate in the rumen and the entry rate of glucose into the body pool of glucose in sheep were measured by isotope-dilution methods. Propionate production rates were measured by using a continuous infusion of specifically labelled [(14)C]propionate. Glucose entry rates were estimated by using either a primed infusion or a continuous infusion of [U-(14)C]glucose. 2. The specific radioactivity of plasma glucose was constant between 4 and 9hr. after the commencement of intravenous infusion of [U-(14)C]glucose and between 1 and 3hr. when a primed infusion was used. 3. Infusion of [(14)C]propionate intraruminally resulted in a fairly constant specific radioactivity of rumen propionate between about 4 and 9hr. and of plasma glucose between 6 and 9hr. after the commencement of the infusion. Comparison of the mean specific radioactivities of glucose and propionate during these periods allowed estimates to be made of the contribution of propionate to glucose synthesis. 4. Comparisons of the specific radioactivities of plasma glucose and rumen propionate during intraruminal infusions of one of [1-(14)C]-, [2-(14)C]-, [3-(14)C]- and [U-(14)C]-propionate indicated considerable exchange of C-1 of propionate on conversion into glucose. The incorporation of C-2 and C-3 of propionate into glucose and lactate indicated that 54% of both the glucose and lactate synthesized arose from propionate carbon. 5. No differences were found for glucose entry rates measured either by a primed infusion or by a continuous infusion. The mean entry rate (+/-s.e.m.) of glucose estimated by using a continuous infusion into sheep was 0.33+/-0.03 (4) m-mole/min. and by using a primed infusion was 0.32+/-0.01 (4) m-mole/min. The mean propionate production rate was 1.24+/-0.03 (8) m-moles/min. The conversion of propionate into glucose was 0.36 m-mole/min., indicating that 32% of the propionate produced in the rumen is used for glucose synthesis. 6. It was indicated that a considerable amount of the propionate converted into glucose was first converted into lactate.     

Salt intake and depletion increase circulating levels of endogenous ouabain in normal men

High-salt diets elevate circulating Na+ pump inhibitors, vascular resistance, and blood pressure. Ouabain induces a form of hypertension mediated via the alpha2-Na+ pump isoform and the calcium influx mode of the vascular sodium calcium exchanger (NCX). Whereas elevated levels of an endogenous ouabain (EO) and NCX have been implicated in salt-sensitive hypertension, acute changes in sodium balance do not affect plasma EO. This study investigated the impact of longer-term alterations in sodium balance on the circulating levels and renal clearance of EO in normal humans. Thirteen normal men consumed a normal diet, high-salt diet, and hydrochlorothiazide (HCTZ), each for 5-day periods to alter sodium balance. EO and other humoral and urinary variables were determined daily. On a normal diet, urinary sodium excretion (140 +/- 16 meq/day), plasma EO (0.43 +/- 0.08 nmol/l) and urinary EO excretion (1.04 +/- 0.13 nmol/day) were at steady state. On the 3rd day of a high-salt diet, urine sodium excretion (315 +/- 28 meq/day), plasma EO (5.8 +/- 2.2 nmol/l), and the urinary EO excretion (1.69 +/- 0.27 nmol/day) were significantly increased, while plasma renin activity and aldosterone levels were suppressed. The salt-evoked increase in plasma EO was greater in older individuals, in subjects whose baseline circulating EO was higher, and in those with low renal clearance. During HCTZ, body weight decreased and plasma renin activity, aldosterone, and EO (1.71 +/- 0.77 nmol/l) rose, while urinary EO excretion remained within the normal range (1.44 +/- 0.31 nmol/day). Blood pressure fell in one subject during HCTZ. HPLC of the plasma extracts showed one primary peak of EO immunoreactivity with a retention time equivalent to ouabain. High-salt diets and HCTZ raise plasma EO by stimulating EO secretion, and a J-shaped curve relates sodium balance and EO in healthy men. Under normal dietary conditions, approximately 98% of the filtered load of EO is reabsorbed by the kidney, and differences in the circulating levels of EO are strongly influenced by secretion and urinary excretion of EO. The dramatic impact of high-salt diets on plasma EO is consistent with its proposed role as a humoral vasoconstrictor that links salt intake with vascular function in hypertension.     

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.     

Formation of androstanediol from 13C-labeled testosterone in humans

The determination of urinary 5 alpha-androstane-3 alpha,17 beta-diol (3a-Diol) by gas chromatography/mass spectometry during and after the infusion of stable-labeled testosterone (T) represents an alternative to the use of radioactive label for turnover studies in vivo. Using this methodology to assess the urinary excretion rates of T and 3a-Diol in healthy men (n = 6) and women (n = 5) during and after the intravenous infusion (t = 4 hours) of 20 mg (men) or 5 mg (women) [13C]testosterone, the cumulative renal excretion of 13C-labeled T was found to be 15.6 +/- 9.6 micrograms/24 hours (men) and 1.1 +/- 1.6 micrograms/24 hours (women), equivalent to 0.08% +/- 0.05% and 0.02% +/- 0.03% of the infused amount of 13C-T, respectively. The cumulative excretion of 13C-3a-Diol was 67.7 +/- 19.9 micrograms/24 hours (men) and 10.0 +/- 6.0 micrograms/24 hours (women), equivalent to 0.3 +/- 0.1% and 0.2 +/- 0.1% of the infused dose of 13C-labeled testosterone, respectively.     

Effect of a chronic infusion of atrial natriuretic peptide on sodium balance in normotensive and two-kidney, one-clip hypertensive rats

We have previously found that chronic infusion of atrial natriuretic peptide (ANP) decreased mean arterial pressure (MAP) by 16% in two-kidney, one-clip (2K-1C) hypertensive rats, and we hypothesized that natriuresis might be modified through the pressure-natriuresis mechanism. We therefore decided to evaluate sodium balance in 2K-1C rats infused with ANP (0.5 micrograms/h for 4 days). The ANP infusion to the 2K-1C rats induced a significant decrease in MAP from 171 +/- 3 to a minimum value of 147 +/- 6 mm Hg after 2 days of treatment (p less than 0.001). Sodium excretion fell from 2,536 +/- 60 to 2,047 +/- 86 (p less than 0.001) and 2,211 +/- 96 mu Eq/24 h (p less than 0.05) by days 1 and 2 of ANP administration. Furthermore, fractional excretion of sodium intake decreased from 99.1 +/- 1.5 to 81.1 +/- 2.9 (p less than 0.001), 84.1 +/- 2.6 (p less than 0.05) and 85.9 +/- 5.15% (p less than 0.05) by days 1, 2 and 3 of ANP infusion, respectively, returning to basal values thereafter. The administration of vehicle (0.9% NaCl) did not induce any significant change in 2K-1C hypertensive rats. The infusion of either vehicle or the same dose of ANP to normotensive rats (0.5 micrograms/h, for 4 days) did not modify sodium balance throughout the experiment. These results strongly suggest that the ANP-induced decrease in MAP might be responsible for the transitory sodium retention observed in 2K-1C hypertensive rats during the administration of the peptide.     

Effect on maternal and fetal renal function and plasma renin activity of a high salt intake by the ewe

The effect on renal function of replacing maternal drinking water with a solution containing 0.17 M NaCl was studied in 9 ewes and their chronically catheterised fetuses over a period of 9 days. Maternal sodium intake increased from control values of 2.19 +/- 0.09 mmol/h to 44.3 +/- 7.4 (P less than 0.001) and 46.3 +/- 6.5 mmol/h (P less than 0.001) on the 3rd and 6th days of salt ingestion. Maternal plasma sodium levels were not affected, but the urinary sodium/potassium ratio increased from 0.15 +/- 0.07 to 2.26 +/- 0.34 (P less than 0.001) after 6 days and plasma renin activity fell from 2.87 +/- 0.76 to 1.00 +/- 0.25 ng/ml per h (P less than 0.05). The changes in maternal sodium intake had no effect on fetal plasma sodium levels nor on fetal plasma renin activity. Sodium excretion and fetal urinary sodium/potassium ratio did not change. However, 3 days after the ewes returned to drinking water fetal plasma renin activity was significantly higher than it was prior to maternal ingestion of 0.17 M NaCl. Fetal plasma renin activity was inversely related to fetal plasma sodium levels (P less than 0.01). The results show that changes in maternal sodium intake had no long term effect on fetal plasma sodium levels nor on fetal renal sodium excretion. The fall in maternal plasma renin activity in the absence of any change in the fetal renin activity, indicates that the fetal renin angiotensin system is controlled by factors other than those influencing the maternal renin angiotensin system. Since fetal urinary sodium/potassium ratios remained unchanged it would suggest that fetal sodium excretion is not influenced by maternal levels of aldosterone.     

Reduced natriuresis after oral sodium load in cholestatic rats: role of compartment volumes and ANP

The purpose of this study was to assess the participation of the atrial natriuretic peptide (ANP)-cGMP system in electrolyte and volume handling of cholestatic rats submitted to an acute oral sodium load. Cholestasis was induced by ligation and section of the common bile duct (n = 51). Control rats were sham operated (n = 56). Three weeks after surgery, 24-hr urinary volume, sodium, potassium, cGMP and creatinine excretion were measured. Three days later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary excretion was measured for 6 hr. In parallel groups of rats, plasma volume, electrolytes and ANP concentration, extracellular fluid volume (ECFV), and renal medullary ANP-induced cGMP production were determined in basal conditions or 1 hr after oral sodium overload. As compared with controls, cholestatic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3.5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic. Cholestatic rats showed higher basal excretion of sodium, potassium, and volume than controls, but equal urinary cGMP. After the NaCl overload, cholestatic rats showed a reduced sodium excretion but equal urinary cGMP. One hr after sodium overload, both groups showed hypernatremia, but whereas in control rats ECFV and ANP increased (50.7 +/- 4.1 pg/ml), in cholestatic rats ECFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ml). ANP-induced cGMP production in renal medulla was similar in cholestatic and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg). One hr after the load, medullary cGMP production rose significantly in both groups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1. 7 fmol/min/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.     

Effect of angiotensin converting enzyme inhibition on renal response to atrial natriuretic factor in rats

Previous studies have shown that atrial natriuretic factor (ANF) inhibits renin secretion whereas cilazapril blocks angiotensin II generation via converting enzyme inhibition. Both agents enhance renal excretory function. The present study was conducted to test whether the renin-angiotension system is involved in the ANF-induced renal effects. ANF was administered to anesthetized normal rats (n = 16) with or without a simultaneous infusion of cilazapril. Single bolus injections of ANF at doses of 2.5 micrograms/kg and 5.0 micrograms/kg significantly decreased mean arterial blood pressure by 6.8 +/- 2.3% and 9.4 +/- 2.2%, respectively. The corresponding increases in glomerular filtration rate were 5.6 +/- 3.7% and 8.4 +/- 2.8%, in absolute sodium excretion were 55.0 +/- 18.5% and 105.2 +/- 39.9%, and in urine flow were 24.8 +/- 9.3% and 35.6 +/- 14.6%. Intravenous infusion of cilazapril (33 micrograms/kg.min) reduced the arterial blood pressure, elevated the glomerular filtration rate and increased sodium and water excretion. The corresponding doses of ANF administration during continuous infusion of cilazapril further decreased blood pressure by 8.3 +/- 1.9% and 10.9 +/- 5.4%, respectively. However, there were no significant changes in the glomerular filtration rate and sodium and water excretion. The failure of ANF to exhibit a renal effect was irrelevant to the lowering blood pressure induced by cilazapril. These results suggest that reduced endogenous angiotensin II generation contributes to the renal, but not the hypotensive, effect of ANF.     

Effect of NH4Cl acidosis on the function of renin-angiotensin-aldosterone system in newborn infants.

The present study was undertaken to assess the influence of acute metabolic acidosis on the activity of renin-angiotensin-aldosterone system and renal function in a group of seven one-week-old neonates with mean birth weight of 2164 g (range: 1300-3750 g) and mean gestational age of 34 weeks (range: 28-40 weeks) undergoing oral NH4Cl load. NH4Cl was given in a dose of 2.8 mEq/kg to evaluate renal acidification. Prior to and following NH4Cl administration blood acid-base parameters, plasma urinary electrolytes, creatinine and aldosterone concentration as well as plasma renin activity, glomerular filtration rate, urine flow rate and net acid secretion were measured. NH4Cl administration significantly depressed blood pH (P < 0.05), total CO2 content (P < 0.01) and base excess (P < 0.01) and resulted in a significant elevation of plasma potassium concentration (P < 0.05). Furthermore, NH4Cl ingestion significantly increased urine flow rate, sodium, chloride and net acid excretion. In response to NH4Cl acidosis no consistent change in plasma renin activity and plasma aldosterone concentration could be detected. There was, however, an about 50% increase in urinary aldosterone excretion from the control value of 4.1 +/- 1.2 micrograms/day to 6.8 +/- 2.3 micrograms/day (P < 0.05) after NH4Cl administration. These data suggest that the responsiveness of neonatal adrenals to stimulation by metabolic acidosis is blunted, acidosis therefore, may play a minor role in the neonatal hyperfunction of renin-angiotensin-aldosterone system.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise effects on chromium excretion of trained and untrained men consuming a constant diet

Chromium excretion of eight trained and five sedentary men was determined on rest days and after exercise to exhaustion at 90% of maximum O2 consumption (VO2max) to determine if degree of physical fitness affects urinary Cr losses. Subjects were fed a constant daily diet containing approximately 9 micrograms Cr/1,000 kcal. VO2max of the trained runners was in the good or above range based on their age and that of the sedentary subjects was average or below. While consuming the control diet, basal urinary Cr excretion of subjects who exercise regularly was significantly lower than that of the sedentary control subjects, 0.09 +/- 0.01 and 0.21 +/- 0.03 microgram/day (mean +/- SE), respectively. When subjects consumed self-chosen diets, basal urinary Cr excretion of the trained subjects was also significantly lower than that of the untrained subjects. Daily urinary Cr excretion of trained subjects was significantly higher on the day of a single exercise bout at 90% VO2max compared with nonexercise days, 0.12 +/- 0.02 and 0.09 +/- 0.01 microgram/day, respectively. Urinary Cr excretion of sedentary subjects was not altered after controlled exercise. These data demonstrate that basal urinary Cr excretion and excretion in response to exercise are related to VO2max and therefore degree of physical fitness.     

Urinary kallikrein excretion after potassium adaptation in the rat

24-h urinary kallikrein excretion in male Sprague-Dawley rats was measured before and after 14 days with 100 mM potassium chloride as drinking fluid ad libitum. Urinary kallikrein excretion increased in K+-adaptation. The increase was greater when the rats were given distilled water rather than 100 mM sodium chloride to drink prior to the potassium chloride. The urinary potassium excretion increased in all rats studied. The urinary sodium excretion, urine volume and fluid intake increased significantly in rats that had distilled water to drink prior to the KCl. In marked contrast, when rats were offered NaCl prior to KCl, the urinary sodium excretion was unaffected while the urine volume and fluid intake decreased significantly. This study shows that prior NaCl intake abolishes the natriuretic and diuretic effects of KCl load and only suppresses the increase in urinary kallikrein excretion. This suggests that K+ secretory activity at the distal tubules is the major determinant of the release of renal kallikrein in the rat.