Changes In Urinary Sodium Excretion Research Articles

Plasma immunoreactive attrial natriuretic peptide and changes in dietary sodium intake in man

Plasma levels of immunoreactive atrial natriuretic peptides (IrANP) have been measured in 8 normotensive subjects during alterations in dietary sodium intake. Subjects were studied on their normal sodium intake (2 days) then on a law sodium intake (7 days, 10 mmols Na +/day) and subsequently on a high sodium intake (14 days, 350 mmols Na +/day with the diets being given in a fixed order. Plasma levels (mean ±S.E.M.) of IrANP on a normal sodium diet were 7.3 ± 0.9 pg/ml; 4.5 ± 0.8 on the 7th day of a low sodium intake and 10.8 ± 1.3; 16.6 ± 3.3; 15.5 ± 4.2; 15.6 ± 2.3 pg/ml respectively or the 1st, 3rd, 10th and 14th day on the high sodium intake. Changes in plasma IrANP were closely associated with changes in urinary sodium excretion. These results suggest that in normal subjects the atrial natriuretic peptides may play an important role in the adaptation to increases in dietary sodium intake both on a short and on a longer term basis.

Effects of ouabain on blood pressure regulation in rats.

In order to test the hypothesis that a circulating inhibitor of the sodium-potassium ATPase pump may cause a concomitant rise in blood pressure and increased sodium excretion, we studied chronic effects of continuous infusion of ouabain, an inhibitor of sodium-potassium ATPase, for up to 6 days on systolic blood pressure and urinary sodium excretion in conscious rats. We also evaluated the effect of this substance in rats with hypertension induced by chronic infusion of norepinephrine. Continuous infusion of ouabain (1.2 mg/kg per day) into the jugular vein by an osmotic minipump did not induce any changes in systolic blood pressure and urinary sodium excretion in intact rats on regular diets. Furthermore it did not cause a change in systolic blood pressure in rats drinking 1% NaCl, and in unilaterally nephrectomized rats drinking 1% NaCl, when compared with vehicle-infused animals. When the same dose of ouabain was administered simultaneously with 1.8 mg/kg per day norepinephrine infused intraperitoneally by another osmotic minipump in conscious rats, systolic blood pressure rose on day 1 to only 129.3 +/- 2.8 mmHg compared with the rist to 145.0 +/- 2.0 mmHg when norepinephrine alone was infused (P less than 0.01). The antihypertensive effect of ouabain was sustained for the entire experimental period lasting for 6 days and was not associated with any changes in urinary sodium excretion. The administration of ouabain to rats made hypertensive by a 3-day infusion of norepinephrine, returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting a further 3 days and was not associated with any changes in urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

High-carbohydrate diet: antinatriuretic and blood pressure response in normal men

The hypothesis that high-carbohydrate feeding leads to increased insulin secretion, sodium retention, and elevation in blood pressure was examined in seven healthy men. A baseline 7-day balance study on low (13%) or high (52%) carbohydrate was followed by a 2-wk balance on the alternate diet and a 1-wk balance on the baseline diet Results indicated that changing carbohydrate intake caused a rapid (2–3 day) inverse change in urinary sodium excretion and balance. By the second week, however, urinary-sodium level returned to baseline accompanied by an inverse change in plasma aldosterone. No significant rise in blood pressure was detected throughout the study. High-carbohydrate feeding promotes sodium retention in normal subjects, but the effect is counterregulated by a reduction in plasma aldosterone. A high-carbohydrate diet in healthy subjects does not cause a significant short-term increase in blood pressure.

Decreased urinary active and inactive kallikrein by chronic infusion of vasopressin in conscious rats.

To assess possible interactions of circulating vasopressin with the synthesis or activation of renal kallikrein, we studied the effect of chronic infusion of vasopressin (7.2 U/kg/day i.p.) for 6 days on the urinary excretion of total and active kallikrein in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after the treatment with trypsin (200 micrograms/ml). Chronic infusion of vasopressin induced sustained decreases in urinary total, active and inactive kallikrein excretion, but did not affect the ratio of active to total kallikrein. The infusion of vasopressin induced significant increases in circulating levels of vasopressin (248.1 +/- 35.2 pg/ml in vasopressin-infused rats (n = 7) compared to 95.5 +/- 14.6 pg/ml in vehicle-infused rats (n = 7), p less than 0.001) and in weight gain (39.6 +/- 1.3 g in vasopressin-infused rats (n = 7) compared to 29.1 +/- 3.3 g in vehicle-infused rats (n = 7), p less than 0.05), and also sustained decreases in water intake and urine volume, but it did not induce any change in urinary sodium excretion. Circulating levels of angiotensin II was decreased by chronic infusion of vasopressin. Thus, the present study suggests that the elevation of circulating vasopressin levels induces a decrease in the synthesis of renal kallikrein.

Importance of the renal nerves in the pathogenesis of experimental hypertension.

Anatomical studies have demonstrated sympathetic innervation of the renal arterioles, juxtaglomerular apparatus, and renal tubules. Physiologic studies of the effects of the renal efferent nerves on renin release and renal sodium handling indicate that they play an important role in body fluid homeostasis and cardiovascular regulation. In addition, evidence is accumulating that stimulation of intrarenal mechanoreceptors and chemoreceptors causes in increase in renal afferent nerve activity and that alterations in renal afferent nerve traffic are, in turn, associated with changes in blood pressure and in vasoconstrictor tone in the contralateral kidney. Further, recent studies have demonstrated functionally significant connections between renal afferent nerves and the central nervous system. Interruption of the renal sympathetic nerves has been shown to prevent or attenuate hypertension in a number of animal models, suggesting that the renal nerves have an important role in the pathogenesis of experimental hypertension. In the spontaneously hypertensive rate of the Okamoto strain (SHR) and the DOCA-NaCl rat, the delay in the development of hypertension produced by renal denervation is due in part to increased sodium excretion thought to be secondary to interruption of the renal efferent nerves. In contrast, in one-kidney, one clip and two-kidney, one clip Goldblatt hypertension in the rat and coarctation hypertension in the dog, the depressor effect of renal denervation is unrelated to changes in urinary sodium excretion or plasma renin activity. In these models the attenuation of hypertension following renal denervation appears to be secondary to a decrease in peripheral sympathetic activity. Evidence in the one-kidney model suggests that interruption of the renal afferent nerves lower blood pressure via an effect on central noradrenergic mechanisms.

Role of renal alpha-adrenoceptors mediating renin secretion.

The increase in renin secretion resulting from low-frequency renal nerve stimulation (0.5 Hz) occurs in the absence of changes in urinary sodium excretion or renal blood flow and is apparently derived from a direct effect of renal sympathetic nerves on juxtaglomerular granular cells. We sought to determine the role of renal alpha-adrenoceptors in this neurally evoked renin secretion. The neurally evoked renin secretion was unaffected by renal alpha-adrenoceptor blockade with phentolamine or prazosin; however, two dose levels of phenoxybenzamine equally inhibited the renin secretion. The renal vasoconstrictor response to graded renal nerve stimulation was similarly diminished by phentolamine, prazosin, and the higher phenoxybenzamine dose, whereas the lower phenoxybenzamine dose was significantly less effective. Renal alpha-adrenoceptor stimulation with methoxamine infusion at doses that were just subthreshold for altering renal blood flow and urinary sodium excretion or at doses that just reduced urinary sodium excretion also did not change renin secretion. Higher doses of methoxamine that decreased both renal blood flow and sodium excretion increased renin secretion. Based on the inability of phentolamine and prazosin to prevent neurally mediated renin secretion and on the dose-response relationship between methoxamine and changes in renin secretion, renal blood flow, and urinary sodium excretion, we conclude that renal alpha-adrenoceptors do not mediate renin secretion elicited by direct neural activation of the juxtaglomerular granular cells. The data suggest that phenoxybenzamine inhibits neurally mediated renin secretion by a mechanism other than renal alpha-adrenoceptor blockade.

Humoral nature of the urine response to simulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors by distending small balloons located at the pulmonary vein--left atrial junctions and in the left atrial appendage was studied in anaesthetized dogs in which bretylium tosylate, atenolol and atropine had been administered to effect blockade of renal nerves and to prevent increases in heart rate resulting from stimulation of atrial receptors. In these dogs, distension of the balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure, and resulted in increases in urine flow, decreases in urinary sodium concentration and no significant changes in urinary sodium excretion. It is concluded that the humoral mechanism is responsible for the diuresis in response to stimulation of atrial receptors and has no significant effect on the response of natriuresis known to involve a decrease in the activity in the renal nerves and haemodynamic changes associated with stimulation of atrial receptors.

Effects of indomethacin on plasma renin activity, plasma aldosterone concentration, urinary prostaglandin E excretion and blood pressure in patients with essential hypertension.

To investigate the interrelationship between the renin-angiotensin-aldosterone system and prostaglandin system, plasma renin activity, plasma aldosterone concentration, urinary sodium excretion, urinary prostaglandin E excretion and blood pressure were determined before and after administration of indomethacin, a prostaglandin synthetase inhibitor, during sodium depletion with furosemide administration and low sodium diets in 11 patients with essential hypertension. With the addition of indomethacin, plasma renin activity decreased from 52.9±8.6 ng/ml to 8.5±1.3 ng/ml, plasma aldosterone concentration from 20.4±3.7 ng/100 ml to 5.4±1.3 ng/100 ml, and urinary prostaglandin E excretion from 330.1±58.8 ng/day to 168.8±32.8 ng/day. Significant positive correlation was found between the change of plasma renin activity and that of urinary prostaglandin E excretion (r=0.73, p<0.01). The addition of indomethacin did not produce any significant change in urinary sodium excretion (from 78.0±10.6 mEq/day to 61.2±11.6 mEq/day); whereas indomethacin administration diminished the hypotensive effects of furosemide administration and low sodium diets. The present results show that renal prostaglandin E may be one of the regulators of renal renin release, and that the use of indomethacin, an antiinflammatory drug frequently prescribed in recent years, may diminish the hypotensive effects of furosemide and other diuretics.

The renin-aldosterone system in exaggerated natriuresis of essential hypertension.

1. The effect of intravenous loading with 500 ml of sodium chloride solution (50 g/l) on plasma renin concentration, plasma aldosterone concentration, urinary sodium excretion and mean blood pressure was studied in 15 young patients with mild essential hypertension and 10 healthy normotensive control subjects. 2. Plasma renin concentration and plasma aldosterone concentration were suppressed to the same degree during loading in both the hypertensive and normotensive groups. Urinary sodium excretion was significantly higher in the hypertensive patients than in the normotensive subjects. Mean blood pressure increased slightly in both groups. 3. Plasma renin concentration and plasma aldosterone concentration were significantly correlated in both groups before sodium loading. The increase in urinary sodium excretion was significantly correlated to the suppression of plasma aldosterone concentration in the hypertensive, but not in the normotensive, group. No correlation was found between changes in urinary sodium excretion and changes in plasma renin concentration or mean blood pressure. 4. The results indicate that the suppressibility of the renin-aldosterone system by hyperosmotic sodium chloride solution is normal in young patients with mild essential hypertension. It is suggested that the changes in plasma aldosterone concentration induced by sodium loading might be involved in the regulation of exaggerated natriuresis in essential hypertension.

Potassium-sparing effect of enhanced renal ammonia production.

The effect of a primary alteration in renal ammonia production on potassium excretion was explored in normal men utilizing ingestion of glutamine to increase ammonia production independent of concomitant acid-base manipulations. After ingesting a constant-formula diet of normal electrolyte content for 3 days, normal men underwent on separate occasions in a rigidly paired fashion an acute study with ingestion of glutamine (4.3 mmol/kg) or only water. Glutamine ingestion under conditions of normal acidification or concomitant with an acute acidifying stimulus resulted in an increase in ammonium and concomitant decrease in potassium excretion. The potassium conservation could not be accounted for by changes in urinary sodium excretion or in plasma potassium or acid-base parameters. Furthermore, when NaHCO3 was ingested for 3 days preceding both the water and glutamine studies, the influence of glutamine on both ammonium and potassium excretion was reduced significantly. These studies suggest that altered ammonia production can affect potassium excretion, providing further evidence in support of a renal potassium-ammonia homeostatic mechanism.

Renal regulation of sodium excretion. Function in health and in edema-forming states

Urinary sodium excretion could be regulated through changes in glomerular filtration rate (GFR) or sodium reabsorption. However, marked changes in GFR may result in only small changes in urinary sodium excretion. This suggests that alterations in sodium excretion result from changes in net sodium reabsorption along the nephron. Several factors play a role in the regulation of sodium excretion, but their relative importance has not been defined perfectly. They include (1) the intrarenal distribution of glomerular filtrate, (2) hormonal effects (aldosterone), (3) peritubular physical factors (hydrostatic and oncotic pressure), and (4) the possible existence of a natriuretic material. Edema-forming states result from the renal retention of salt and water. In these states, the rate of sodium and water excretion is less than the rate of entry of salt and water. Thus, the kidneys are responsible for salt and water retention.

Renal Regulation of Sodium Excretion

Urinary sodium excretion could be regulated through changes in glomerular filtration rate (GFR) or sodium reabsorption. However, marked changes in GFR may result in only small changes in urinary sodium excretion. This suggests that alterations in sodium excretion result from changes in net sodium reabsorption along the nephron. Several factors play a role in the regulation of sodium excretion, but their relative importance has not been defined perfectly. They include (1) the intrarenal distribution of glomerular filtrate, (2) hormonal effects (aldosterone), (3) peritubular physical factors (hydrostatic and oncotic pressure), and (4) the possible existence of a natriuretic material. Edema-forming states result from the renal retention of salt and water. In these states, the rate of sodium and water excretion is less than the rate of entry of salt and water. Thus, the kidneys are responsible for salt and water retention.

A dissociated effect of Amino-Glutethimide on the mineralocorticoid secretion in man

Amino-Glutethimide (AG) decreases the secretion rates of aldosterone in control subjects. DOC secretory rate changes are less consistent (with an increase in 3 out of 5) and 18-OH DOC increases evidently in all 5 subjects where measured. Urinary sodium excretion increases after AG. With dexamethasone added to AG to suppress the compensatory increase in ACTH, the DOC and 18-OH DOC secretion rates decrease to the initial levels and further sodium diuresis occurs. Similar changes in urinary sodium excretion occurred in two hypertensive patients, but the blood pressure decreasing effect of AG was not consistent. These results indicate that zonal differences in the response of the adrenal cortex to AG probably exist. The zona glomerulosa, producing aldosterone, is more susceptible to the inhibitory action of AG, while other mineralocorticoids from the zona fasciculata (18-OH DOC and, in part, also DOC) increase as a consequence of the compensatory increase in ACTH. The combination of AG and dexamethasone may prove as a useful tool in suppressing the excessive mineralocorticoid secretion.

Hormonal factors influencing salt appetite in lactation.

SummaryThe appetite of wild rabbits (Oryctolagus cuniculus (L)) for 500 mEq/1 solutions of NaCl, KCl, MgCl2, and CaCl2, was studied during daily injections of ovine prolactin, ovine growth hormone or synthetic oxytocin. The animals were individually caged and external sodium balances were made. Under all experimental conditions the animals were obtaining ample sodium from the food, as evidenced by a substantial urinary sodium excretion. Injection of 50 I.U. prolactin significantly increased NaCl intake from a control value of 0·4 mEq/day to 2·3 mEq/day during the course of injections. CaCl2 intake was also significantly increased. The mean daily intake of NaCl during the oxytocin treatment was 1·34 mEq/day, 21/2; times the control value. Water intake was reduced but there were no significant changes in the intakes of KCl, MgCl2 and CaCl2,. Growth hormone had no effect on electrolyte or H2O intakes.Previously reported work shows that a significant increase in NaCl intake occurs during lactation in the wild rabbit. The metabolic studies indicate that, as in lactation, the increase in NaCl intake witb prolactin and oxytocin occurs without any preceding change in urinary sodium excretion. The results suggest that the increase in NaCl intake in lactation is hormonal in origin and not caused by the sodium requirements of lactation.

BLOOD-VOLUME CHANGES AND TRANSFUSION REQUIREMENTS OF BURNED PATIENTS AFTER THE SHOCK PHASE OF INJURY

The blood-volume was measured after the shock phase (first 48 hours after injury) in a group of patients with major burns. Selection was made of those who, despite a positive sodium balance, had a persistently low urinary sodium excretion, on the ground that underperfusion might be a cause of this phenomenon. Normal-to-low blood-volumes were found, associated with a failure to expand the plasma-volume to compensate for a redcell deficit. The volume of transfused blood required to produce clinical evidence of adequate peripheral tissue perfusion ( a) exceeded calculated deficits, (b) in some cases caused a higher than normal central venous pressure, and (c) resulted in an increase in urinary sodium excretion. Haemoglobin levels bore no relation to blood-volume deficits or to transfusion requirements. It is concluded that chronic underperfusion may be an important cause of persistence of the sodium retention phase following injury, and that the two most useful guides to transfusion requirements in burned patients after the shock phase are (1) clinical estimation of peripheral tissue perfusion assessed in a warm environment, and (2) changes in urinary sodium excretion.