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Ethanol diuresis in rats: possible modifying factors.

Ethanol has been shown to produce a biphasic dose-dependent effect on urine output in rats. Experiments were carried out to examine factors which may influence ethanol diuresis. Immobilization stress (30 min) decreased and ethanol (2.5 g kg-1) increased urine output of intragastrically hydrated rats. In stressed rats, ethanol had a more pronounced diuretic effect compared with home cage control rats. This increased sensitivity to ethanol disappeared when rats were immobilized daily for four days, indicating development of tolerance. The diuretic action of ethanol was not influenced by adrenalectomy.

Adrenalectomy↗

The adenosine receptor antagonist, 8-phenyltheophylline, causes diuresis and saliuresis in the rat.

The diuretic and adenosine antagonist actions of two alkylxanthines have been compared in the conscious rat. 8-Phenyltheophylline (10 mg kg-1) antagonized adenosine-induced bradycardia in the rat for at least 3 h whereas enprofylline (10 mg kg-1) had no effect on this response. 8-Phenyltheophylline (10 mg kg-1) evoked diuresis and saliuresis in the rat whereas enprofylline (10 mg kg-1) had no effect on excretory parameters. These results indicate that the diuretic action of some alkylxanthines may be related to adenosine antagonism.

Adenosine↗

The role of renal nerves in the diuresis and natriuresis caused by stimulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium, was studied in anaesthetized dogs in which on kidney had been surgically denervated. In these dogs diuretic and natriuretic responses to stimulation of atrial receptors were obtained in the denervated and the intact kidney; both responses were significantly greater in the intact kidney than in the denervated kidney. In the denervated kidney the natriuretic response showed a significant correlation to increases in heart rate resulting from stimulating of atrial receptors. It is concluded that the renal nerves contribute significantly to the increases in urine flow and sodium excretion in response to stimulation of atrial receptors. In the denervated kidney, the diuresis appeared to be mediated by a humoral mechanism and the natriuresis was associated with concomitant increases in heart rate.

Animals↗

Diuresis from stimulation of left atrial receptors: initial purification steps from plasma of the causative agent.

This paper reports the initial purification steps of a humoral agent which may mediate the diuresis resulting from stimulation of left atrial receptors in anaesthetized dogs. The agent was shown to be stabilized in plasma by acidification to pH 3.2. Acid acetone precipitation was found to be a convenient method as a first stage in the purification of the humoral agent in plasma. Heat stability studies showed that the agent was stable in acidified plasma for up to 20 min of heating in a boiling water bath. Precipitation of plasma proteins under these conditions made this another possible first stage in the purification of the agent in plasma. Some general conclusions about the possible nature of the humoral agent are discussed.

Animals↗

Diuresis from stimulation of left atrial receptors in dogs: further purification of the causative agent from plasma.

Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by an unknown humoral agent. This paper reports the further purification from plasma of acetone extracts of the humoral agent which may mediate the diuretic response. Activity of the humoral agent was detected using the Malpighian tubules of Rhodnius prolixus. Gel filtration of the acetone extracts on Sephadex G-25 and G-100, followed by dialysis of the fraction from Sephadex G-100 that contained the humoral agent, showed that the activity of the agent was associated with a high molecular weight fraction (greater than 30000). Acetone extracts of the humoral agent were also shown to be stable to treatment with HCl for 1 h at 25 degrees C. After this acid treatment, gel filtration on Sephadex gels and Bio-Gel P-2 showed that the agent was of low molecular weight (less than 1800). It is concluded that the activity of the humoral agent, as detected by the Malpighian tubule preparation, is associated with a molecule of low molecular weight which may be bound to a larger molecule from which it can be dissociated by acid treatment.

Animals↗

Water diuresis in the domestic fowl.

1. The exteriorization of ureters in domestic fowls allows the collection of urine uncontaminated by faeces.2. When water is administered by stomach tube to a fowl, water is stored in the crop, from which it is slowly released into the proventriculus.3. Immediately after water gavage, there is a sharp rise of urine flow accompanied by an increase in endogenous creatinine excretion and a fall in the osmolarity of the urine. This initial increase in urine flow is of short duration, and is followed by a normal curve of diuresis with a peak at about 90 min after hydration.4. The first rise in urine flow following the filling of the crop appears to be of reflex origin, as distension of the crop with paraffin produces an enhanced excretion of urine and of creatinine.5. Changes in urine flow and in creatinine excretion are closely correlated.6. After water deprivation for 18 hr, the urine is slightly hyptertonic to blood. The maximum urine concentration observed was of the order of 600 m-osmole/l.

Animals↗

The time course of changes in renal tissue composition duruig water diuresis in the rat.

1. The time course and extent of changes in the composition of renal tissue slices in water diuresis were determined by sacrificing groups of rats before and during the intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer over 2 hr, and subsequently to maintain for up to 7(1/2) hr, a positive fluid load of 4% body weight.2. The corticomedullary osmolal gradient characteristic of the nondiuretic rats was progressively dissipated until, at 7(1/2) hr, only papillary tip concentrations were higher than those of other segments.3. The changes in individual constituents followed different time courses: (i) an increase in water content in all segments, particularly the papilla, was almost complete by 1 hr, preceding the maximal increases in urine flow; (ii) a marked decrease in papillary and medullary urea content in the first hour was followed by a slower, progressive decrease leading to an almost complete dissipation of the urea gradient by 7(1/2) hr; (iii) small, non-significant decreases in sodium content occurred in all segments in the first hr, followed by a further small, progressive decrease in papillary sodium content; (iv) changes in ammonium and potassium concentrations were mainly related to those in water content, since the contents of these solutes showed only small changes.4. By 2 hr, differences in the rates of decline of osmolal and urea concentrations in urine and papilla led to urinary concentrations significantly lower than papillary values. The steep papilla-urine urea concentration difference became smaller, but remained significant even at 7(1/2) hr.5. The findings are discussed in terms of changes in countercurrent mechanisms, particularly as influenced by anti-diuretic hormone.6. The development of papilla/urine urea concentration ratio greater than unity is also considered in terms of passive transport with changes in membrane permeability.

Ammonia↗

Influence of prehydration on the changes in renal tissue composition induced by water diuresis in the rat.

1. The composition of renal tissue was determined in rats before and immediately after intravenous infusion of dextrose (2.5 g/100 ml.) in amounts sufficient to administer a positive fluid load of 4% body weight over 2 hr. The rats were classified into three groups, according to the preinfusion urine osmolality: hydropaenia, normal and moderately diuretic (over 2400, 800-1500 and below 800 mu-osmoles/g H(2)O, respectively).2. In non-infused rats, the steepness of the corticomedullary osmolal gradient varied, due to differences in both water and solute (sodium and urea) contents, and was related to urinary osmolality. Whereas differences in medullary and papillary solute contents occurred between all three groups, papillary water content was significantly higher only in the moderately diuretic animals.3. Dextrose infusion caused the induction of water diuresis, the lowest urinary osmolalities being produced in the previously moderately diuretic animals.4. Dextrose infusion caused a considerable reduction in the steepness of the corticomedullary osmolal gradient in all rats, particularly in the previously hydropaenic animals, due to changes in both solute (sodium and urea) and water contents. Whereas reductions in medullary and papillary solute contents occurred in all three groups, there was no further increase in papillary water content from the already high values seen in the noninfused diuretic animals.5. Thus, dextrose infusion largely abolished any previous differences in tissue water content, whereas significant, though small, differences in osmolal (particularly urea) content persisted.6. These data are discussed in terms of changes and differences in endogenous antidiuretic hormone (A.D.H.) release.7. Changes in the magnitude and direction of the urinary-papillary urea concentration difference are discussed in terms of passive transport, with probable A.D.H.-induced changes in nephron urea permeability.

Animals↗

Increased urinary kallikrein excretion during prostaglandin E1 infusion in anaesthetized dogs and its relation to natriuresis and diuresis.

. The effect of intra-arterial prostaglandin E1 (PGE1) infusion on urinary kallikrein, sodium, potassium and water excretion was studied in normal anaesthetized dogs. 2. Infusion of PGE1 caused a dose-related increase in urinary excretion of kallikrein, sodium, potassium and water as well as an increase in renal blood flow (R.B.F.) and a fall in urinary osmolality and renal vascular resistance. 3. The changes occurred in the absence of appreciable changes in inulin clearance (Cin), arterial blood pressure, haematocrit, and plasma sodium and potassium concentrations. 4. The increased urinary kallikrein excretion correlated positively with the natriuresis, diuresis and kaliuresis and the increase in renal blood flow, but negatively with the urinary osmolality and renal vascular resistance. 5. It is concluded that renal kallikrein is involved in the renal response to arterial infusion of PGE1.

Animals↗

Assessment of proximal tubular sodium reabsorption during water diuresis in patients with heart disease.

In order to examine the relation between cardiac state and the capacity to excrete a water load, 10 normal subjects and 61 patients with heart disease were studied during water diuresis. Under these conditions, urine flow approximates to the rate of delivery of filtrate, and therefore of sodium, from the proximal tubule of the kidney to the loop of Henle, while free water clearance is a function of distal sodium reabsorption. In 12 patients with complete heart block, ventricular pacing was associated with increased urine flow and free water clearance. Oral propranolol in 3 normal subjects and in 9 patients with intact atrial septa caused a reduction, and oral practolol in 4 normal subjects and 8 patients caused no change. In 6 patients with atrial septal defect, propranolol was without effect. Maximum urine flow correlated with left ventricular end-diastolic pressure but not mean left atrial pressure in 16 patients with chronic rheumatic heart disease. In 7 patients with ischaemic heart disease, maximum urine flow was higher than in those with chronic rheumatic heart disease and similar increase in left ventricular end-diastolic pressure. These results reflect a close relation between proximal tubular sodium reabsorption and cardiac state, and suggest that inappropriate sodium reabsorption at this site may contribute to fluid retention in heart disease.

Acetanilides↗

Birmingham Medical Research Expeditionary Society 1977 Expedition: the diuresis and related changes during a trek to high altitude.

Continuous 24-hr urine collections were made by 17 subjects during a trek to 5400 m. Fluid intake was recorded by diary. Weight and fat folds were measured daily. The results were compared with daily measurements of packed cell volume (PCV) and reticulocyte count. Early fluid retention was matched by a fall in PCV. There was a diuresis with negative fluid balance towards the end of the ascent and again early in descent. There was a slight trend for fluid retention to occur in those most affected by acute mountain sickness but the effect was not marked.

Adult↗

Effect of renal denervation, furosemide, and acute saline loading on postobstructive diuresis in the rat.

The effect of acute or chronic renal denervation, furosemide, or acute saline loading on the postobstructive diuresis (POD) which occurs after relief of 24-h bilateral ureteral obstruction (BUO) was studied in anaesthetized rats. Acute renal denervation during POD 1--2 h after relief of BUO had no effect on glomerular filtration rate of sodium, potassium, water, or solute excretion, in contrast with its natriuretic and diuretic effect in sham-operated rats. Intravenous furosemide or acute saline loading caused a further marked increase in sodium and water excretion during POD, demonstrating the ability of the kidney undergoing POD to respond to other types of natriuretic stimuli. Chronic renal denervation prior to BUO had no effect on subsequent POD. The lack of response of the BUO kidney undergoing POD to acute denervation contrasts with the changes in renal function following denervation of the unilateral postobstructive kidney. The results indicate that the kidney undergoing POD after relief of BUO may be functionally denervated and suggest that inhibition of renal nerve activity could contribute to the pathophysiology of POD.

Animals↗

Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig.

The synthesis of 17 alpha-acetoxy-3 beta-[(beta-D-glucopyranosyl)oxy]- 6 alpha-methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20 beta-hydroxy-3 beta-[(alpha-L-rhamnopyranosyl)oxy]-5 beta, 14 beta-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14 beta-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit [3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes.

Animals↗

Glucagon and diuresis in the treatment of ureteral calculi.

Intravenous glucagon and diuresis caused by diagnostic doses of sodium diatrizoate were used to treat 5 patients with ureteral colic and urographic findings consistent with partial obstruction by a ureteral calculus. Pain was relieved and the calculus passed within two hours in 4 patients and within eight hours in the fifth. No complications were noted.

Adult↗

Pressure diuresis and natriuresis in cirrhotic rats.

Arterial hypotension in liver cirrhosis has been proposed as a major mechanism contributing to renal sodium and water retention. To evaluate kidney excretory responses at different levels of arterial pressure (AP), we have characterized the relationships between renal perfusion pressure (RPP) and sodium and water excretion in carbon tetrachloride cirrhotic rats. Experiments were performed in anesthetized control (n = 9) and cirrhotic rats with (Asc, n = 6) and without ascites (Cir, n = 6) by mechanically adjusting vascular resistance in animals with renal denervation and infused with main systemic hormones. Control and Cir animals showed similar glomerular filtration rates (GFR), renal blood flows, hematocrits (Hct), and plasma proteins (PP). However, Hct, PP, and GFR were significantly lower in the Asc rats. For the same level of RPP, both cirrhotic groups excreted significantly less water and sodium than controls. Then, the pressure diuresis and natriuresis relationships of the Cir animals were significantly depressed, but those of the Asc animals were more reduced than those of the Cir rats. These results indicate that the cirrhotic kidney is not able to normally increase the sodium and water excretion in response to changes in AP. Intrarenal mechanisms, and not mainly RPP, are likely mediators of the renal alterations of liver cirrhosis.

Animals↗

Temporal differences in bladder dysfunction caused by diabetes, diuresis, and treated diabetes in mice.

Diabetic bladder dysfunction is a common complication of diabetes mellitus (DM) with poorly understood natural history. This study examined the temporal changes in bladder function 3, 9, 12, and 20 wk after induction of DM by streptozotocin (STZ) in male C57BL/6 mice compared with that in age-matched diabetic mice treated with insulin, 5% sucrose-induced diuretic mice, and sham-treated control mice. Conscious cystometrograms of mice were examined in addition to the measurements of micturition cycle. Diabetes resulted in decreased body weight. Bladder weight, urine output, bladder capacity, and compliance increased in the DM and diuretic groups. Peak voiding pressure (PVP) increased initially in both DM and diuretic mice. However, in DM mice, PVP dropped dramatically at and after 12 wk. Similar changes in the capacity, compliance, and emptying ability of the bladder were seen during the first 9 wk of the diabetes or diuresis, whereas significant decline in the emptying ability of the bladder was only seen in diabetes after 12 wk of disease in mice. Long-term insulin replacement effectively reversed most changes in bladder function. These results suggest that the transition from a compensated to a decompensated bladder dysfunction occurs 9-12 wk after induction of DM in mice by STZ.

Animals↗

Atrial stretch-induced diuresis in Brattleboro rats.

Inflation of a balloon at the superior vena caval/right atrial junction of the conscious Brattleboro rat initiated a rapid and significant diuresis, natriuresis, and kaliuresis (urine volume increased from 20.8 +/- 0.8 to 28.5 +/- 1.3 ml/h, P less than 0.005; urine sodium increased from 2,417 +/- 115 to 3,510 +/- 230 mu eq/h, P less than 0.005; urine potassium increased from 351 +/- 52 to 478 +/- 58 mu eq/h, P less than 0.05; n = 6). Bilateral renal denervation did not significantly alter this response. Since the Brattleboro rat is totally deficient in antidiuretic hormone (ADH) and since inflation of the balloon causes no change in blood pressure, the reflex increase in urinary salt and water output must be mediated, at least in part by a blood-borne factor other than ADH.

Angioplasty, Balloon↗

Vasopressin modulation of medullary blood flow and pressure-natriuresis-diuresis in the decerebrated rat.

Studies in our laboratory and others have demonstrated that arginine vasopressin (AVP) exerts potent vasoconstrictor actions on the vessels supplying the renal medulla. The physiological importance of these vascular effects of AVP has been difficult to assess because of high endogenous levels of AVP in anesthetized, surgically prepared animals. We have developed a decerebrated, hypophysectomized, renal-denervated rat model that enables us to study the effects of low levels of AVP on the pressure-diuresis, relationship under acute conditions. These rats maintain normal mean arterial pressure (MAP) and plasma AVP (2.5 pg/ml). Cortical and medullary blood flow (CBF and MBF, respectively) were measured by laser-Doppler flowmetry and total renal blood flow (RBF) by transit time flowmetry. Renal interstitial fluid pressure (RIFP) and urinary sodium excretion (UNaV) responses were determined during controlled increases of MAP produced by aortic occlusion below the renal arteries. From a baseline of 97 +/- 2 mmHg, 30% increases in MAP resulted in a 63% increase in MBF, 35% increase in RIFP, and sixfold increase in UNaV, whereas CBF and RBF remained unchanged. Infusion of AVP (0.50 ng.kg-1.min-1, which increased plasma AVP from normal control levels of 3 pg/ml to 11 pg/ml) produced no change in baseline MAP, RBF, or CBF but lowered MBF by 24%, RIFP by 26%, and UNaV by 71%. The slope of the relationship of AP and UNaV, MBF, and RIP was reduced to nearly zero by these small increases of plasma AVP. We conclude that an increase of plasma AVP in the range that occurs with water restriction decreases MBF selectively and greatly attenuates the arterial pressure-MBF and pressure-natriuretic relationship.

Animals↗