Reduction In Urinary Sodium Excretion Research Articles

The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects.

The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio-hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio-hGH administration and safety parameters were monitored over a 3-week period. Growth hormone levels reached a mean (+/- SD) peak of 106 +/- 10 mIU/l at 3.3 +/- 0.5 h following the first dose and resulted in a significant rise of somatomedin C. free fatty acids, fasting blood glucose and insulin concentrations. Bio-hGH administration resulted in a significant increase in body weight (80.0 +/- 4.5 to 81.1 +/- 4.3 kg; P less than 0.01) which was associated with a marked reduction in urinary sodium excretion (196 +/- 38 to 45 +/- 20 mmol/day; P less than 0.025). Serum T3 increased during bio-hGH administration and was associated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio-hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40 U/m2/week) or more in patients with GH responsive short stature.

Effects of calcitonin gene-related peptide on renal blood flow in the rat.

The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.

Role of atrial peptide system in renal and endocrine adaptation to hypotensive hemorrhage.

Hypotensive hemorrhage (HH) is characterized by intravascular volume depletion, avid renal sodium retention, and activation of the renin-angiotensin-aldosterone system (RAAS). The current studies were designed to investigate whether intravascular volume depletion would modulate circulating atrial natriuretic factor (ANF) and, further, to examine what contribution, if any, a decrease in ANF would have in mediating the antinatriuresis and RAAS stimulation associated with HH. Two groups of anesthetized dogs underwent controlled arterial hemorrhage to reduce mean arterial pressure by 15-20 mmHg. Data were collected before and immediately after HH. One group (n = 6) underwent hemorrhage alone, whereas a second group (n = 5) underwent HH with simultaneous administration of alpha-human ANF (2.5 ng.kg-1.min-1), a dose calculated to prevent a reduction in ANF. In the untreated group, circulating ANF was significantly reduced after hemorrhage (79.4 +/- 7.4 to 57.2 +/- 3.4 pg/ml, P less than 0.05), whereas in the treated group ANF increased significantly (73.5 +/- 12.2 to 147.4 +/- 17.2 pg/ml, P less than 0.05). Despite differences in circulating ANF, both groups had similar reductions in urinary sodium excretion and renal blood flow, and similar increases in plasma renin activity. These studies demonstrate that circulating ANF is significantly reduced in HH; however, the mechanism of antinatriuresis and activation of the RAAS is independent of the reduction in circulating ANF.

The Effects of Aprotinin, a Kallikrein Inhibitor, on Renin Release and Urinary Sodium Excretion in Mild Essential Hypertensives

The effects of aprotinin on renin release and renal function were evaluated in 24 male essential hypertensive patients, on unrestricted (n = 17) and on chronic low as well as on high sodium intake. Aprotinin (1 X 10(6) kallikrein inhibitor units) or saline (200 ml) were infused in all patients for 6 h. Blood samples were taken for plasma renin activity (PRA) and 6-h urine collections were obtained for active and inactive kallikrein, sodium and potassium excretion measurement. In patients on unrestricted sodium diet, aprotinin had no effect on blood pressure (BP), glomerular filtration rate, renal plasma flow, urinary sodium and potassium excretion. However, an inverse relationship was found between pretreatment urinary sodium excretion and the per cent reduction of the latter after aprotinin. A significant reduction in urinary sodium excretion was induced by aprotinin in patients on high sodium intake, whereas no change was observed in the same patients when on a low sodium diet. Aprotinin reduced the urinary excretion of active kallikrein by 81% and the active to total kallikrein ratio from 24 to 6%. Infusion of aprotinin induced a significant decline in active renin but did not modify inactive renin levels in patients on unrestricted sodium diet as well as in patients on low or high sodium intake. Our data suggest that the inhibition of kallikrein and/or other serine proteases by aprotinin can interfere with renal release of active renin and also support the hypothesis that the renal kallikrein system exerts a regulatory control on sodium excretion in salt replete hypertensives.

Effects of Hydrochlorothiazide and Amiloride in Renal Hypophosphatemic Rickets

The effects of thiazide diuretics on serum phosphate concentration, renal tubular threshold for phosphate, and urinary calcium excretion in children with renal hypophosphatemic rickets were studied. There were nine controlled acute studies conducted in five patients, and, in addition, seven long-term studies of up to 26 months were performed. During the acute studies, the children continued to receive the same doses of oral calcitriol and phosphate supplementation as at home. Hydrochlorothiazide, 1.50 to 2.25 mg/kg/d, was used alone in the first four studies; hydrochlorothiazide and amiloride at a dose of 1 mg for each 5 mg of hydrochlorothiazide were used in the other five studies. Administration of the diuretics for four days gave rise to a significant increase in serum phosphate concentration from 3.1 +/- 0.4 mg/dL to 3.7 +/- 0.9 mg/dL (P less than .01) and in tubular threshold for phosphate from 1.31 +/- 0.45 mg/dL to 1.74 +/- 0.60 mg/dL (P less than .01). These changes were accompanied by significant reductions in urinary sodium excretion from 135 +/- 39 mEq/24 h during the control period to 99 +/- 42 mEq/24 h on the fourth day of therapy (P less than .05), fractional sodium excretion from 0.99% +/- 0.42% to 0.81% +/- 0.42% (P less than .05), and urinary calcium excretion from 57.3 +/- 28.9 mg/24 h to 19.0 +/- 13.1 mg/24 h (P less than .01). Fractional excretion of phosphate divided by fractional excretion of sodium after the treatment with diuretics was not significantly different from that observed at the end of the control period. Increments in serum phosphate concentrations were correlated with elevations in serum albumin concentrations (r = .739; P less than .02). As an additional index of intravascular volume contraction, the elevations in serum phosphate concentrations were correlated with the increase in BUN, (r = .793; P less than .01). The addition of amiloride in the last five studies prevented the hypokalemia and alkalosis that had complicated the administration of hydrochlorothiazide. Long-term follow-up studies for a total of 119 therapy-months on six children and one adult, who continued to receive the diuretics concomitantly with calcitriol and phosphate supplementation, showed that they were free of complications except for a transient episode of hypercalcemia and hypercalciuria in one patient. In comparison with the previous period of treatment with calcitriol and phosphate without diuretics, linear growth velocity and healing of the rickets were not changed in two children and improved in the other four after the addition of hydrochlorothiazide and amiloride.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of hypoxemia on sodium and water excretion in chronic obstructive lung disease

To determine the role of hypoxemia in the pathogenesis of Impaired sodium and water excretion in advanced chronic obstructive lung disease, 11 clinically stable, hypercapneic patients requiring long-term supplemental oxygen were studied. The renal, hormonal, and cardiovascular responses to sodium and water loading were determined during five-and-a-half-hour studies on a control day (arterial oxygen tension = 80 ± 6 mm Hg) and on an experimental day under hypoxic conditions (arterial oxygen tension = 39 ± 2 mm Hg). Hypoxemia produced a significant decrease in urinary sodium excretion but did not affect urinary water excretion. Hypoxemia also resulted in concomitant declines in mean blood pressure, glomerular filtration rate, and filtered sodium load. Renal plasma flow and filtration fraction were unchanged whereas cardiac index rose. On the control day, plasma renin activity and norepinephrine levels were elevated whereas aldosterone and arginine vasopressin levels were normal; none of these four hormones was affected by hypoxemia. Renal tubular function did not appear to be altered by hypoxemia as there was no significant change in fractional reabsorption of sodium. The concurrent decreases in glomerular filtration rate, filtered sodium load, and mean blood pressure at constant renal plasma flow suggest that the reduction In urinary sodium excretion was due to an effect of hypoxemia on glomerular function, possibly related to impaired renovascular autoregulation.

An impedance cardiographic study of the mechanism of blood pressure fall after moderate dietary sodium restriction.

Impedance cardiography was performed on 13 free-living subjects to determine the mechanism which ties modest sodium restriction to a reduction in blood pressure. During salt restriction intervention, significant decreases in systolic and diastolic blood pressure (6 and 7 mmHg) were observed associated with mild reduction in urinary sodium excretion from 176 to 85 mmol/day. The impedance cardiogram demonstrated a significant decrease in stroke volume (12 ml), which was related to a fall in diastolic pressure (r = 0.59, p less than 0.05). In the further analysis of individual parameters in Kubicek's formula calculating stroke volume, thoracic impedance (Zo/L) showed a significant increase during salt restriction and a change (delta) in ln L/Zo related significantly to delta ln diastolic pressure in linear multiple regression analysis. As thoracic impedance has been reported to reflect intrathoracic fluid content, a decrease in extracellular fluid volume was suggested as a possible mechanism of the fall in blood pressure even with modest sodium restriction.

本態性高血圧症に対する塩分制限と体重減少の効果

We set out to establish whether dietary sodium restriction is feasible and effective in the treatment of essential hypertension on general practice.Fifty-six patients with mild to moderate essential hypertension in outpatient clinic, whose average blood pressure was 169±20/103±8.9mmHg and average relative body-weight was 1.25 (range 0.93-1.95) were allocated to 3 groups by the reduction of urinary sodium-excretion and/or bodyweight after the dietary instruction for hypertension. These patients on non-medication for hypertension were randomly instructed on how to reduce sodium intake or energy intake by metabolic ward dietician. He checked the patients about the compliance of dietary instruction using a questionnaire, and a change of urinary sodium-excretion and body weight at every 6 weeks for 12 weeks.50% of the patients, whose 24-hour urinary sodium-excretion were decreased without a decrease in body-weight, were effective on blood pressure. In 7 of 8 effective patients, 24-hour urinary NaCl-excretion before instruction were 12g or more and the magnitude of a reduction of urinary NaCl excretion was more than 3g/day.On the other hand, only 30% of patients whose body-weight decreased without a decrease in sodium-excretion, were effective on systolic pressure. But urinary sodium-excretion in this group increased, especially that in non-effective patients was higher than in effective patients and plasma aldosterone in non-effective patients significantly decreased from 10.0±2.6 to 8.5±3.4ng/dl (p<0.05).68.8% of patients with decrease in both sodiumexcretion in urine and body-weight were effective, especially frequency of the patients with decrease in diastric pressure was significantly high (χ2=5.11, p<0.05). Though plasma aldosterone level did not change after decrease in both sodium excretion and body-weight, plasma insulin level significantly decreased in only effective patients (p<0.05).In 26 of all patient with decrease in body weight, fasting plasma insulin level were 7μU/ml or more before dietary instruction. 12 of 15 patients, whose plasma insulin level decreased in 2μU/ml or more after dieary instruction, were decreased in blood pressure.Conclusion: The dietary salt restriction which were reducted by 3g/day or more may be effective to hypertension when hypertensive patients have over 12g/24-hour urinary NaCl excretion. But it may be necessary in an effectiveness of diastric hypertension to make body weight reduction and the effect of weight-reduction on hypertension appeared when relatively high concentration of plasma insulin make decrease.

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats.

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to 'mental stress' in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during 'rest' and during a 20 min period of 'mental stress'. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64 +/- 5%) than in WKY (-34 +/- 7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during 'mental stress' the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e.g. the renal and splanchnic regions during increased alertness.

Blood pressure, renal and metabolic effects of ACTH in normotensive man.

1. The blood pressure, renal and metabolic effects of adrenocorticotropic hormone (ACTH) have been studied in six normotensive subjects and two patients with Addison's disease on maintenance steroid therapy. 2. In normotensive subjects, 5 days ACTH treatment (0.5 mg 12 hourly) was associated with a rise in systolic blood pressure and mean arterial pressure. There was a small rise in diastolic pressure but no consistent change in heart rate. Plasma sodium increased and plasma potassium fell. Serum creatinine and urea concentrations were unchanged. Fluid intake increased and urine output was unchanged but ACTH withdrawal was associated with a diuresis. There was an initial reduction in urinary sodium excretion and a natriuresis after ACTH withdrawal. Plasma volume and body weight rose. 3. ACTH produced increases in plasma cortisol, 11-deoxycortisol, corticosterone, deoxycorticosterone, aldosterone, 17 alpha-hydroxyprogesterone and 17 alpha,20 alpha-dihydroxyprogesterone. Plasma renin concentration fell. 4. Patients with Addison's disease showed no change in blood pressure or in any other metabolic variable studied. 5. The effects of ACTH in man resembled those found in sheep.

Control of canine renin release: macula densa requires prostaglandin synthesis.

1. The macula densa mechanism of renin release was functionally isolated in uninephrectomized, anaesthetized dogs by producing renal denervation, beta-adrenoceptor blockade, and maximum renal vasodilation with an infusion of papaverine into the renal artery. 2. A suprarenal aortic clamp was adjusted to reduce renal perfusion pressure by 50% which resulted in a 90% reduction in urinary sodium excretion and a two to threefold increase in plasma renin activity within 10 min. 3. Indomethacin (8 mg/kg) or meclofenamic acid (10 mg/kg) inhibited the rise plasma renin activity produced by the decrease in renal perfusion pressure in this model, although a comparable decrease in urinary sodium excretion was achieved. 4. We conclude that the macula densa mechanism of renin release is blocked by inhibition of prostaglandin synthesis.

Metabolic studies in a patient with a phaeochromocytoma associated with hypokalaemia and hyperaldosteronism.

SUMMARY A case of phaeochromocytoma with hypokalaemia, hyperaldosteronism, normal cortisol production and normal urinary corticosteroid excretion is described. Both α-adrenergic blockade and combined α and β blockade resulted in marked antidiuresis with urinary sodium and potassium retention and a rise in plasma volume. Combined α and β blockade led to some reduction in the high aldosterone production rate. The hypokalaemia was corrected by α-adrenergic blockade. After operative removal of the tumour the aldosterone production rate was normal. The marked reduction in urinary sodium excretion in response to α-adrenergic blockade, if reproducible in other cases of phaeochromocytoma, might be a useful test for the presence of a phaeochromocytoma.