Relationship of urinary kallikrein excretion to urinary potassium excretion during furosemide administration with and without amiloride

The relationship of urinary kallikrein excretion to urine volume, and to urinary sodium and potassium excretions was studied in normal rats during furosemide diuresis and superimposed injection of amiloride, a K+-sparing diuretic. Continuous infusion of furosemide increased urinary kallikrein, sodium and potassium excretions and the urine volume. Amiloride injection during furosemide diuresis caused further increase in diuresis and natriuresis, but a prompt decrease in urinary kallikrein excretion to basal level, and potassium excretion to below the basal level. The significant correlation of urinary kallikrein excretion to urinary potassium excretion, but not to urine volume and urinary sodium excretion after amiloride injection suggests that the major determinant of urinary kallikrein excretion is renal potassium secretion through a mechanism that is affected by amiloride.     

Study on the diuretic activity of Strychnos potatorum Linn. seed extract in albino rats.

Methanol extract of Strychnos potatorum Linn. seeds (SPSE) was evaluated for its diuretic activity in Wistar albino rats. The SPSE was administered at the graded doses of 200, 400, and 600 mg/kg body weight. The parameters which were taken into account during the experimental on each rat were: total urine volume (corrected for water intake during the test period), body weight before and after the experiment, and the concentration of sodium, potassium, and chloride ions in urine. The total urine volumes of the SPSE (600 mg/kg)-treated rats were evaluated nearly two and half fold then compared with the control (saline treated) group. Excretion of cations (sodium and potassium ions) and anions (chloride ions) also increased significantly with respect to the control group. The diuretic effect was comparable with that of the standard drug Furosemide. The increase of cations in the urine on treatment with Strychnos potatorum seed extract (SPSE) was dose-dependent. This effect supports the use of the Strychnos potatorum seeds as a diuretic in folk remedies.     

Sinusoidal 50 Hz 500 μT magnetic field has no acute effect on urinary 6-sulphatoxymelatonin in wistar rats

The effect of a 50 Hz, vertical magnetic field on the excretion of urinary 6-sulphatoxymelatonin (aMT6s) of male and female Wistar rats was studied in a self-controlled experiment. Twenty rats were kept in metabolic cages under 9:15 h light:dark conditions. The urine of the animals was collected twice per day for 5 consecutive days. The concentration of aMT6s in the rat urine was measured by ¹²⁵I radioimmunoassay. The rats were exposed to 5 and 500 μT flux density for 24 h. The excretion of urinary aMT6s did not show significant changes during or after magnetic field exposure. © 1995 Wiley-Liss, Inc.     

One week of exposure to 50 Hz, vertical magnetic field does not reduce urinary 6-sulphatoxymelatonin excretion of male wistar rats

The effect of exposure to 100 or 50 microT, 50 Hz, vertical magnetic field on the excretion of 6-sulphatoxymelatonin (6SM) in the nocturnal urine of rats was studied. Twelve male Wistar rats were kept under 12:12 hr light:dark conditions. The nocturnal urine of animals was collected in metabolic cages over 4 consecutive weeks. The concentration of 6SM in the rat urine was measured by 125I radioimmunoassay and normalized to creatinine concentration. After the first week of urine collection, 6 rats were exposed to 100 microT or 50 microT flux density magnetic fields (MF) for 8 hr daily for 1 week. It was found that the excretion of the primary metabolite of melatonin in the urine, 6SM, did not show statistically significant changes during and after magnetic field exposure.     

Study on the diuretic activity of Strychnos potatorum Linn. seed extract in albino rats

Methanol extract of Strychnos potatorum Linn. seeds (SPSE) was evaluated for its diuretic activity in Wistar albino rats. The SPSE was administered at the graded doses of 200, 400, and 600 mg/kg body weight. The parameters which were taken into account during the experimental on each rat were: total urine volume (corrected for water intake during the test period), body weight before and after the experiment, and the concentration of sodium, potassium, and chloride ions in urine. The total urine volumes of the SPSE (600 mg/kg)-treated rats were evaluated nearly two and half fold then compared with the control (saline treated) group. Excretion of cations (sodium and potassium ions) and anions (chloride ions) also increased significantly with respect to the control group. The diuretic effect was comparable with that of the standard drug Furosemide. The increase of cations in the urine on treatment with Strychnos potatorum seed extract (SPSE) was dose-dependent. This effect supports the use of the Strychnos potatorum seeds as a diuretic in folk remedies.     

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.     

Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats

Diuretic and uricosuric properties have traditionally been attributed to corn silk, stigma/style of Zea mays L. Although the diuretic effect was confirmed, studies of the plant's effects on renal function or solute excretion were lacking. Thus, we studied the effects of corn silk aqueous extract on the urinary excretion of water, Na+, K+, and uric acid. Glomerular and proximal tubular function and Na+ tubular handling were also studied. Conscious, unrestrained adult male rats were housed in individual metabolic cages (IMC) with continuous urine collection for 5 and 3 h, following two protocols. The effects of 25, 50, 200, 350, and 500 mg/kg body wt. corn silk extract on urine volume plus Na+ and K+ excretions were studied in water-loaded conscious rats (2.5 ml/100 g body wt.) in the IMC for 5 h (Protocol 1). Kaliuresis was observed with doses of 350 (100.42 +/- 22.32-120.28 +/- 19.70 microEq/5 h/100 g body wt.; n = 13) and 500 mg/kg body wt. (94.97+/- 29.30-134.32 +/- 39.98 microEq/5h/100 g body wt.; n = 12; p<0.01), and the latter dose resulted in diuresis as well (1.98 +/- 0.44-2.41 +/- 0.41 ml/5 h/100 g body wt.; n = 12; p<0.05). The effects of a 500 mg/kg body wt. dose of corn silk extract on urine volume, Na+, K+ and uric acid excretions, and glomerular and proximal tubular function, were measured respectively by creatinine (Cler) and Li+ (ClLi) clearances and Na+ tubular handling, in water-loaded rats (5 ml/100 g body wt.) in the IMC for 3 h (Protocol 2). Clcr (294.6 +/- 73.2, n = 12, to 241.7 +/- 48.0 microl/ min/100 g body wt.; n = 13; p<0.05) and the Na+ filtered load (41.9 +/- 10.3, n = 12, to 34.3 +/- .8, n = 13, p<0.05) decreased and ClLi and Na+ excretion were unchanged, while K+ excretion (0.1044 +/- 0.0458, n=12, to 0.2289 +/- 0.0583 microEq/min/100 body wt.; n = 13; p<0.001) increased. For Na+ tubular handling, the fractional proximal tubular reabsorption (91.5 +/- 3.5, n = 12, to 87.5 +/- 3.4%; n = 13; p<0.01) decreased, and both fractional distal reabsorptions--I and II--increased (96.5 +/- 1.5, n = 12, to 97.8 +/- 0.9%; n = 13; p<0.01; and 8.2 +/- 3.5, n = 12, to 12.2 +/- 3.4%, n = 13, p<0.01, respectively). To summarize, in water-loaded conscious rats (2.5 ml/100 body wt.), corn silk aqueous extract is diuretic at a dose of 500 mg/kg body wt. and kaliuretic at doses of 350 and 500 mg/kg body wt. In water-loaded conscious rats (5.0 ml/100 g body wt.), corn silk aqueous extract is kaliuretic at a dose of 500 mg/kg body wt., but glomerular filtration and filtered load decrease without affecting proximal tubular function, Na+, or uric acid excretion.     

Urinary 6-sulphatoxymelatonin excretion is increased in rats after 24 hours of exposure to vertical 50 Hz, 100 μT magnetic field

The effect of exposure to a 50 Hz, vertical magnetic field on the excretion of urinary 6-sulphatoxymelatonin (aMT6s) of rats was studied in a self-controlled experiment. Ten male Wistar rats were kept under 9:15 h light:dark conditions in metabolic cages. The rats were exposed to 1.0 or 100 μT flux density for 24 h. The excretion of aMT6s, which is the primary metabolite of melatonin in the urine, did not show a statistically significant decrease, as measured by ¹²⁵I radioimmunoassay, during or after magnetic field exposure of rats to either flux density. At 100 μT flux density, the increase of aMT6s excretion on the day after exposure was statistically significant (P < .02), compared with the value under exposure, but was not significant compared with the baseline values before exposure. Bioelectromagnetics 18:190–192, 1997. © 1997 Wiley-Liss, Inc.     

No effect of isolation on blood pressure and daily electrolyte excretion in rats

The effects of isolation stress on mean blood pressure (BP) and on body weight, water and food intake as well as on urine flow, urinary sodium and potassium excretion were studied in CFY and Long Evans rats. During a 7 day isolation period, food and water intake as well as urine flow, urinary sodium and potassium excretion, as expressed for 100 g body weight, were not changed in either group. Body weight increased similarly in isolated (38 +/- 2 g) and aggregated (41 +/- 5 g) CFY rats. Compared to group housed rats, BP in male CFY animals was not increased after a 7 day isolation (111 +/- 3 vs 111 +/- 3 mmHg, NS). In additional experiments high sodium intake by physiological saline drinking slightly elevated blood pressure but failed to induce arterial hypertension in isolated rats (118 +/- 2 vs 121 +/- 3 mmHg, NS). We conclude that, contrary to some reports from other laboratories, isolation stress has no detectable effect on BP and/or water and electrolyte balance.     

Urinary excretion of furosemide in rats with HgCl2-induced acute renal damage.

To examine the influence of mercuric chloride (HgCl2)-induced acute renal damage on urinary excretion of furosemide, HgCl2 (1 mg/kg) or its vehicle alone was given intraperitoneally to Wistar rats. The following two experiments were done. Study I: Three percent body weight (b.w.) of 1% NaCl solution or furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally before and after HgCl2 treatment, and an 8-hour urine was collected. Study II: Furosemide (30 mg/kg) was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-beta-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl2-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl2 were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl2-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl2-induced acute renal damage.     

High Dosage Metolazone in Chronic Renal Failure

Metolazone is a modified quinazolinesulphonamide and in a dose of between 4 and 7·5 mg is an effective diuretic in man with normal renal function. Fourteen patients with non-oedematous stable chronic renal failure (creatinine clearance ranging from 1·2 to 12 ml/min) were given metolazone in doses ranging from 20-150 mg. A noticeable increase in urine flow and sodium excretion occurred, free water clearance increased, and there was a small but significant increase in potassium excretion. No side effects were noted.     

Long-Term Responses to Loss of Renal Mass: Tubular Changes: Potassium Adaptation After Reduction of Nephron Population

Two weeks after 75 percent nephrectomy in rats fed a normal diet glomerular filtration rate was found to be reduced by 2/3 and there was no hyperkalemia. Normal K balance was maintained by a threefold increase of fractional urinary potassium excretion. When infused with 0.5 M KCl solution, both normal and 75 percent nephrectomized rats increased their fractional excretion, while normal rats kept on a very high K-diet did not further increase their fractional potassium excretion. Adaptation of fractional excretion to infused KCl was blunted in 75 percent nephrectomized rats given a low K diet.Addition of 0.1 M KCl to the drinking water resulted in a three- to fourfold increase of potassium intake in normal rats: within 7 days, the Na-K-ATPase in the outer medulla of the kidney rose by 30 percent but no change occurred in the cortex. Further increases in dietary K load induced an increase of Na-K-ATPase activity, both in outer medulla and cortex, but not in other tissues. After 75 percent nephrectomy, specific Na-K-ATPase activity increased by 20-25 percent in the outer medulla and in the cortex.Dietary K loading, in normal rats, also resulted in a large increase of net potassium secretion into the perfused colon and of specific Na-K-ATPase activity of the colonic mucosa. These effects of potassium loading were not abolished by adrenalectomy and were accompanied by an increase of transmural PD. It was concluded that chronic potassium loading may enhance secretion of potassium into lower nephron tubular fluid and into colonic contents by primarily stimulating the synthesis of Na-K-ATPase and the resulting increase of the number of pumping sites. 75 percent nephrectomy may induce similar changes in the remaining nephrons.     

Mild hypertension: a clinical trial conducted in hospital general practice.

To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice. They received bendrofluazide and potassium chloride or bendrofluazide, potassium chloride, and reserpine according to a double-blind crossover protocol, and blood biochemical values were studied over eight weeks and six months. When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone. The blood pressure values measured by the general practitioners were similar to those measured in hospital. Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures. Although plasma renin activity increased on diuretic treatment, continued treatment did not produce a further increase, and levels gradually declined towards normal.     

Tracheal relaxant and cardiostimulant actions of xanthines can be differentiated from diuretic and CNS-stimulant effects. Role of adenosine antagonism?

Theophylline (1, 3-dimethylxanthine) and enprofylline (3-propylxanthine) have been examined for effects in the rat. Enprofylline was 3.8 times as potent as theophylline as a tracheal relaxant in vitro, and 1.3 times as potent as theophylline to increase the rate of isolated perfused hearts. An oral dose (5 mg/kg) of enprofylline to rats was almost completely recovered in the urine as unchanged drug, showing that this xanthine is well absorbed and negligibly metabolised. Theophylline (10 and 30 mg/kg p.o.) significantly and dose-dependently increased locomotor activity in rats whereas the same doses of enprofylline were without effect on behaviour. Theophylline ( 5-20 mg/kg p.o.) produced significant and dose-dependent natriuretic and volume diuretic effect with little augmentation of potassium excretion. Enprofylline up to 10 mg/kg was without diuretic effects. At the large dose of 20 mg/kg enprofylline decreased sodium excretion and produced some volume diuresis. It is suggested that lack of diuretic and CNS-stimulant behavioural effects by enprofylline is due to its low ability to antagonise adenosine receptor stimulation. Pharmacodynamic differences between enprofylline and the potent adenosine antagonist theophylline may indicate a functional importance of endogenous adenosine.     

Circulating antidiuretic hormone in the X-irradiated rat

Male rats exposed to 500 R of whole-body x-irradiation were allowed food and water ad libitum and housed in metabolism cages; water and food intake and urinary and fecal excretion were recorded daily. Urine output increased 200% during the first 24 hours after irradiation. No significant changes occurred in daily sodium, potassium, urea, or total solute excretion, although calcium excretion approximately doubled after irradiation. The marked increase in free water excretion implicates antidiuretic hormone (ADH) in this phenomenon. Application of a sensitive bioassay for ADH permitted measurement of plasma ADH concentrations in undisturbed, unanesthetized rats before and after irradiation. ADH levels were lower and frequently not detectable 24 hours after exposure. High ADH levels, however, could be provoked in irradiated rats by hemorrhage, indicating that the receptor cells and secretory ability of the posterior pituitary remained intact. Furthermore, irradiated rats responded normally to small intravenous injections (4 to 8 microU) of exogenous ADH. Rats with congenital diabetes insipidus given daily injections of Pitressin showed no postirradiation diuresis. Lastly, increased urinary calcium excretion may result from hypercalcemia which is known to induce diuresis through calcium-vasopressin antagonism. These results further suggest that the diuretic response is due to decreased circulating ADH.     

Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na(+) excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Delta = 12.2 +/- 2.4 mmHg), urine flow (Delta = 54 +/- 8 microliter. min(-1). g(-1)), and Na(+) excretion (Delta = 11.5 +/- 1.9 mueq. min(-1). g(-1)). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na(+) excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na(+) excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na(+) excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.     

Diuretic, natriuretic and hypotensive effects of synthetic atrial natriuretic factor in conscious newborn calves

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.     

阿霉素肾病大鼠肌肉和静脉注射心钠素基因利尿作用的比较研究

为探讨心钠素基因经体细胞转移对阿霉素诱导的肾病动物泌尿功能的影响及其治疗肾病的潜力,采用肌肉或静脉内直接注射裸DNA的方法,将人心钠素基因的逆转录病毒载体分别导入阿霉素肾病动物体内,以期为其提供持续性的心钠素来源。结果发现,人心钠素基因经肌肉和静脉内直接注射这2 种途径导入后,均可使阿霉素肾病动物的尿量/体重比明显增加,有效利尿作用时间大于15d。试验期间,实验组肾病动物的体重明显增长,血浆中的心钠素浓度在基因转移5d 后明显升高,但动物尿中的K⁺和Na⁺浓度无明显变化。以上结果说明,心钠素基因经肌肉和静脉2 种途径导入均可明显改善肾病动物的泌尿功能,具有治疗肾病的潜力。     

The effect of barbiturates on 24-h water intake and renal excretion of sodium and water in dogs

The effects of barbiturates on 24-h intakes of water and food and urinary excretion of sodium and potassium as well as on plasma concentration of sodium and potassium and osmolality were examined in dogs placed in metabolism cages and fed with a semiliquid diet. Administration of barbiturates stimulated drinking in a Series of 8 dogs having free access to water. Twenty four-h water intake and water balance increased significantly. Food intake, urinary output and urinary excretion of solutes, sodium and water did not change in this Series. A significant decrease in urine output as well as in osmolal clearance and urinary excretion of sodium was observed in a Series of 7 dogs having water restricted for 24 h following administration of barbiturates. Water balance increased in this Series. The same restriction of water in the dogs which had not received barbiturates did not modify renal excretion of water and electrolytes. Plasma osmolality, sodium and potassium concentrations did not change in either Series of experiments. It is concluded that barbiturates induce positive water balance either by stimulation of drinking when water is freely available or by reduction in urine output when water is restricted. The results suggest that expansion of the body fluids following the increased water intake may abolish reduction in urine output and sodium excretion which otherwise occur after administration of barbiturates.     

Renal effects of dopamine and ANP in high volume expanded rats

Both dopamine (DA) and atrial natriuretic peptide (ANP) have been postulated to exert similar effects on the kidney, participating in the regulation of body fluid and sodium homeostasis. In the present study, experiments were performed in anesthetized and isotonic sodium chloride volume expanded rats. After acute volume expansion at 15 % of body weight during 30 min, glomerular filtration rate, urine output, sodium excretion, fractional sodium excretion, proximal and distal sodium excretion and blood pressure were measured. In additional groups we administered ANP or haloperidol or the combination of both to volume expanded animals. Blockade of DA receptors with haloperidol, attenuated diuretic and natriuretic responses to volume load. Proximal sodium excretion was not modified by haloperidol in all experimental groups of rats. Reduction in distal tubular excretion was induced by haloperidol in saline infusion expanded rat but not in ANP treated expanded animals. In conclusion, when exaggerated volume expansion is provoked, both DA and ANP exert renal tubular events, but ANP have a major central role in the regulation of renal sodium handling.