Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]

The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.     

An increase in the excretion of total protein and albumin by the human kidney during water diuresis

The rate of excretion of the total protein and albumin during an increase in diuresis after water loading was studied in healthy volunteers. In the control period, the excretion of protein (7.3–11.1 mg/2 h) and albumin (0.29–0.42 mg/2 h) was within of the physiological norm range. Water loading (20 ml/kg) caused water diuresis, urine formation rate increased by a factor of 15, and the reabsorption of solute-free water changed into its excretion. The increase in diuresis was accompanied by a statistically significant increase in the urinary protein and albumin excretion, as well as by an increase in the protein-to-creatinine ratio. After water loading, the excretion of total protein, as compared to the initial period, increased by a factor of 8.4, and of the albumin excretion, by a factor of 2.8, exceeding the generally accepted limits of the norm. The role of intraglomerule hemodynamics in the development of physiological proteinuria related to water diuresis is discussed.     

Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.     

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.     

RNAi-mediated gene knockdown and in vivo diuresis assay in adult female Aedes aegypti mosquitoes

This video protocol demonstrates an effective technique to knockdown a particular gene in an insect and conduct a novel bioassay to measure excretion rate. This method can be used to obtain a better understanding of the process of diuresis in insects and is especially useful in the study of diuresis in blood-feeding arthropods that are able to take up huge amounts of liquid in a single blood meal. This RNAi-mediated gene knockdown combined with an in vivo diuresis assay was developed by the Hansen lab to study the effects of RNAi-mediated knockdown of aquaporin genes on Aedes aegypti mosquito diuresis. The protocol is setup in two parts: the first demonstration illustrates how to construct a simple mosquito injection device and how to prepare and inject dsRNA into the thorax of mosquitoes for RNAi-mediated gene knockdown. The second demonstration illustrates how to determine excretion rates in mosquitoes using an in vivo bioassay.     

Diuresis after a bloodmeal in female Anopheles freeborni

Female Anopheles freeborni discharge urine rapidly and copiously for a brief time after taking a meal of blood. This diuresis begins immediately upon cessation of feeding and continues for about 30 min at a constant rate. A decline in this rate follows and diuresis is completed by 50 min after feeding. This time-course of diuresis is independent of the size of the meal; diuresis after large meals occures at a higher rate, not over a longer time, than diuresis after small meals. Heat-stable and saline-soluble substances that induce rapid excretion by isolated Malpighian tubules can be extracted from the head and thoracic nervous system, suggesting the presence of a neurosecretory diuretic hormone similar to that found in other blood-sucking insects. Decapitation or section of the ventral nerve cord abolishes the rapid phase of diuresis after a bloodmeal. Therefore, in analogy to the situation in the tsetse fly, the head is required either as the source of a diuretic hormone or as link in the pathway that stimulates its release.     

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (ED(NaCl)) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, ED(NaCl) fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED(NaCl) increased by 3.6 mM, (P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.     

The function of innervated kidneys during stimulation of the carotid chemoreceptors under constant renal perfusion pressure]

The carotid chemoreceptors of narcotized, vagotomized and spontaneously breathing hydropenic cats in hypertonic mannite diuresis were stimulated by perfusion with venous blood penic cats in hypertonic mannite diuresis were stimulated by perfusion with venous blood for 70 min. Elevation of blood pressure at the innervated kidneys was prevented by an automatically controlled balloon located within the aorta. Stimulation of the chemoreceptors intensified respiration and raised the arterial systemic pressure. With the renal arteries at constant pressure, the effective renal plasma flow and the glomerular filtration rate significantly declined. The filtration fraction remained unchanged. The absolute urinary and sodium excretion did not change significantly, whereas the fractional time-volume, fractional sodium excretion, and the fractional osmotic excretion significantly increased. The fractional tubular reabsorption of osmotically free water was significantly enhanced. These reactions subsided during subsequent perfusion of the glomerula carotici with arterial blood. The results suggest that tubular sodium reabsorption is inhibited by stimulation of the carotid chemoreceptors, although re-adjustment of renal perfusion and filtrate volume cannot be excluded.     

Diuresis or urinary alkalinisation for salicylate poisoning?

Forty-four adults with aspirin poisoning were treated with oral fluids only, standard forced alkaline diuresis, forced diuresis alone, or sodium bicarbonate (alkali) alone. Alkali alone was at least as effective and possibly more effective than forced alkaline diuresis in enhancing salicylate removal. Unlike the diuresis regimens it did not cause fluid retention or biochemical disturbances. The renal excretion of salicylate depends much more on urine pH than flow rate, and forced diuresis alone had little useful effect. In overdosage aspirin causes sodium and fluid retention and may impair renal function. Attempts to force a diuresis are potentially hazardous and the spurious fall in plasma salicylate concentration caused by haemodilution gives a false impression of efficacy. Further studies are required to determine the optimum treatment for salicylate poisoning.     

Renal effects of acute nitric oxide and ET(A)/ET(B) receptor inhibition in conscious spontaneously hypertensive rats

The aim of the present study was to investigate the effects of endogenous endothelin on renal excretory function in spontaneously hypertensive rats (SHR) after inhibition of NO synthesis. The effects of non-selective ET(A)/ET(B) receptor blockade on L-NAME-induced changes in renal excretory function and blood pressure (BP) were investigated in conscious, SHR and normotensive Wistar rats with implanted catheters in the bladder for urine collection, in the femoral artery for BP registration and in the femoral vein for L-NAME and bosentan administration. L-NAME increased systolic, mean and diastolic BP, diuresis, sodium and chloride excretion (p < 0.01) in both normotensive and hypertensive rats but bosentan returned the values of diuresis, sodium and chloride excretion to control level without any changes in BP in normotensive rats. In SHR the effects of L-NAME were reduced after bosentan (p < 0.05) but the values of diuresis, sodium and chloride excretion still remained statistically significant as compared to control level despite the fact that bosentan lowered mean and diastolic BP increased due to L-NAME administration. Endogenous endothelins participate in a different manner in the rise of BP and in the changes in renal excretory function that develops after L-NAME-induced NO synthase inhibition in normotensive rats and in SHR.     

Pressure diuresis mechanism in the control of renal function and arterial pressure

Precise knowledge of the interrelationships between arterial pressure and urinary excretion of sodium and water is crucial to understanding the long-term control of arterial pressure. Although increases in renal perfusion pressure have been known for more than 35 years to inhibit tubular reabsorption, the mechanism of this pressure diuresis response, the humoral or physical factors involved, and even the nephron segments in which the changes in tubular function occur remain relatively unknown. This review focuses on the experimental evidence that supports current hypotheses concerning the mechanism of pressure diuresis. Specifically, it examines the possibility that pressure diuresis is caused by a small increase in glomerular filtration rate, alterations in the humoral or physical factors regulating proximal tubular reabsorption, and/or inhibition of tubular reabsorption in deep nephrons secondary to changes in hemodynamics in juxtamedullary nephrons. The concept originally proposed that the kidney serves as the dominant long-term controller of arterial pressure is largely based on the assumptions that the pressure diuresis phenomenon exists and that it occurs via a nonadaptive mechanism. It has been proposed that hypertension can develop only if the relationship between arterial pressure and sodium excretion is shifted toward higher pressures. The remainder of this review examines recent evidence indicating that an abnormality in the pressure natriuresis relationship may be associated with the development of hypertension in humans and in the genetic rat models of the disease.     

Effect of diuretics on the distribution and renal excretion of lithium in rats of different ages

The postnatal development of the renal lithium elimination is maturated earlier than that of renal sodium excretion. The filtered lithium is reabsorbed to a great amount in the kidney (70-80%). 90% of the administered lithium is eliminated by the kidney. Acetazolamide stimulates the renal lithium excretion in young and adult rats. Other diuretics with different sites of attack are not able to influence the elimination of lithium. Also, a forced diuresis does not change the elimination rate of lithium. The well-known interactions between sodium and ithium must have their cause in extrarenal processes.     

Effect of single dose of diuretics on renal magnesium excretion in man, with special reference to their site of action.

The administration of a single dose of furosemide, ethacrynic acid and polythiazide to healthy individuals under conditions of maximum water diuresis produces a significant increase in renal magnesium excretion. Elevated Mg excretion displayed a direct correlation to renal sodium excretion after furosemide (r=0.689, p less than 0.001), ethacrynic acid (r=0.869, p less than 0.001) and polythiazide (r=0.586, p less than 0.01). The slopes of the various regression lines did not differe significantly from each other or from the slope of the regression line characterizing this correlation for mannitol (r= 0.603, p less than 0.01). A significant linear correlation was likewise found between the excretion of Mg and total osmotically active substances after furosemide (r=0.783, p less than 0.001), ethacrynic acid (r=0.88, p less than 0.001) and polythiazide (r=0.646, p less than 0.01). The regression lines of the given correlations did not differ significantlyfrom each other, but their slopes were significantly higher than that of the regression line for the correlation after mannitol (r=0.454, p less than 0.01). The findings indicate that tubular Mg transport is influenced both by a decrease in tubular Na resorption in the diluting segment (polythiazide) and by an effect on Na resorption in the parts of the nephron proximal to the diluting segment of the nephron (furosemide, ethacrynic acid).     

Role of prostaglandin E2 in regulation of urine excretion in saluresis, water and osmotic diuresis in rat

In the saluresis, water and osmotic diuresis were indicating an increase of prostaglandin E2 excretion and a correlation between this index and diuresis. Unselective blockade of cyclooxygenase by diclofenac-natrium leads to a decrease of diuresis in the observed types of urine-production in rats. Inhibition of inducible cyclooxygenase by celebrex didn't change the value of diuresis after water load or administration of osmotic agent, but decreased the diuretic effect of furosemide.     

Normotensive normoxic men undergoing water diuresis fail to respond to stimulation of their peripheral arterial chemoreceptors by almitrine with an increase in plasma concentrations of atrial natriuretic factor

The purpose of this study was to investigate the possible participation of atrial natriuretic factor (ANF) in the natriuretic and diuretic response occurring after stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in normoxic humans. The experiments were performed in 14 healthy male volunteers undergoing water diuresis. Each subject participated in two experiments. In one of them they ingested 100-mg almitrine at 12 p.m. The other study served as a control. Surprisingly, our subjects responded to almitrine with an elevation of urine flow only, whereas sodium excretion remained almost unchanged over the whole period of the experiments. As regards ANF plasma concentrations, no statistically significant differences between the control and the almitrine group could be observed. Moreover, no direct connection between ANF plasma concentrations and renal volume excretion was detectable. We conclude that a specific stimulation of peripheral arterial chemoreceptors by almitrine in humans undergoing water diuresis did not seem to raise ANF plasma concentrations as is the case at high altitude. Therefore we would suggest that there exists no specific reflex influence of these receptors on ANF release.     

High urine flow rate increases prostaglandin E excretion in the conscious dog

Although previous studies from this and other laboratories have shown that urinary prostaglandin E excretion (U_PGEV) can vary independent of urine flow rate, recent studies during water diuresis in the conscious dog have suggested that high urine flow rate per se may increase U_PGEV. To examine the effect of urine flow rate on U_PGEV we administered either mannitol, chlorothiazide or Ringer's solution to mongrel dogs and measured U_PGEV. During anesthesia neither mannitol or chlorothiazide increased U_PGEV. There was, however, a consistent increase with all three agents in awake animals. This increase in U_PGEV was independent of alterations in glomerular filtration rate. There was a consistent increase in urinary sodium excretion and decrease in urinary osmolality with all three agents. The changes in PGE, however, were similar to those found during water diuresis when no increase in sodium excretion was found. It is not presently clear whether these findings reflect a true increase in renal PGE synthesis due to some change in flow or pressure within the renal medulla or rather represent unchanged PGE synthesis by renal tubular cells, the high tubule fluid flow rate causing increased entry into the tubular lumen in contrast to the renal interstitium.     

The temperature hysteresis of water-salt metabolism in the frog Rana temporaria]

Frogs acclimated to 4 degrees C were transported to a medium with temperature 20 degrees C, which caused polyuria; recovery of normal diuresis took about 24 h. During this period, hypernatremia was observed together with the increase in natriuresis, the rate of renal excretion of potassium ions with urea remaining constant. Water content of skeletal muscles decreased. Transportation of frogs acclimated to 20 degrees C into a medium with a temperature 4 degrees C decreased their diuresis. Renal excretion of sodium, calcium and magnesium ions remained unchanged, whereas that of potassium ions significantly decreased. The content of potassium and magnesium in the blood serum increased, that of sodium--decreased. Hydratation of muscled and kidneys was accompanied by the decrease of calcium, potassium and magnesium ions calculated per wet weight of the tissues, the level of sodium remaining unaffected. The data obtained indicate significant changes in the pattern of water and salt metabolism in frogs during temperature hysteresis.     

Effects of atrial natriuretic peptides and furosemide in conscious dogs

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.     

Attenuated renal responses to atrial natriuretic factor in streptozotocin-induced diabetic rats

To determine whether the renal responses to atrial natriuretic factor (ANF) are altered in the diabetic state, the diuretic and natriuretic responses to ANF (0.25 microgram.kg-1.min-1, i.v.) were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Urine flow and sodium excretion were measured before and after ANF from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, i.p.) control and DIA rats (Sprague-Dawley rats injected with vehicle or STZ 65 mg/kg, i.p., respectively, 2 weeks prior to the experiment). Blood glucose levels were significantly elevated in the DIA group compared with the control group. ANF produced a significantly blunted diuresis and natriuresis in DIA rats compared with control rats. In addition, reducing the hyperglycemia in DIA rats by treatment with insulin (third group) reversed the blunted urine flow and sodium excretion responses to ANF. This study demonstrates that (i) there is a blunted natriuresis and diuresis to ANF in the STZ-induced DIA rats, and (ii) restoring the glucose levels to normal by insulin treatment in the DIA rats normalized the renal responses to ANF.     

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.