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Many experimental protocols in rodents require the comparison of groups that are fed different diets. Changes in dietary electrolyte and/or fat content can influence food intake, which can potentially introduce bias or confound the results. Unpalatable diets slow growth or cause weight loss, which is exacerbated by housing the animals in individual metabolic cages or by surgery. For balance studies in mice, small changes in body weight and food intake and low urinary flow can amplify these challenges. Powder food can be administered as gel with the addition of a desired amount of water, electrolytes, drugs (if any), and a small amount of agar. We describe here how the use of gel food to vary water, Na, K, and fat content can reduce weight loss and improve reproducibility of intake, urinary excretion, and blood pressure in rodents. In addition, mild food restriction reduces the interindividual variability and intergroup differences in food intake and associated variables, thus improving the statistical power of an experiment. Finally, we also demonstrate the advantages of using gel food for weight-based drug dosing. These protocols can improve the accuracy and reproducibility of experimental data where dietary manipulations are needed and are especially advisable in rodent studies related to water balance, obesity, and blood pressure.

The renal sympathetic nerves operate early during development, influencing renal growth and modulating changes in renal water and electrolyte excretion during transition from fetal to newborn life. Furthermore, they contribute to the important rise in plasma renin activity postnatally.

The effects of single and multiple injections of aldosterone and dexamethasone on renal Na+-K+-ATPase, in vitro renal gluconeogenesis, and urinary electrolyte excretion were examined in adrenalectomized rats in a dose-dependent manner. Single maximal and supramaximal doses of aldosterone (defined by the effect of electrolyte excretion) had no effect on Na+-K+-ATPase or gluconeogenesis. By contrast, a single administration of dexamethasone (in a dose range that increased fasting blood sugar, stimulated renal gluconeogenesis, and had no mineralocorticoid effects) yielded clear-cut activation of Na+-K+-ATPase. Multiple submaximal doses of dexamethasone produced quantitatively similar stimulation of Na+-K+-ATPase and gluconeogenesis. Multiple supramaximal doses of aldosterone stimulated Na+-K+-ATPase and gluconeogenesis, but maximal and submaximal doses of the hormone were without effect. Aldosterone had no effect on hepatic Na+-K+-ATPase or gluconeogenesis. These results suggest that activation of renal Na+-K+-ATPase can be considered a putative glucocorticoid (not mineralocorticoid) effect. Renal Na+-K+-ATPase activation by chronic aldosterone treatment may be mediated by glucocorticoid receptor sites and, hence, may not represent a genuine mineralocorticoid effect.

Aqueous vasopressin was infused to bicarbonate- and glucose-loaded dogs and to nonloaded antidiuretic dogs in doses of 50 mU/kg per min or 50 mU/kg per h. Both doses caused a marked increase in sodium, chloride, and water excretion. The larger dose raised the fractional excretion (sodium clearance (C-Na)/glomerular filtration rate (GFR) times 100) of these ions from 2% or less to in excess of 20%. Blocking the pressor effects of these doses of vasopressin with sodium nitroprusside did not alter the marked natriuretic and chloriuretic effect. The maximal rate of bicarbonate and glucose reabsorption was not depressed by vasopressin infusion; fractional phosphate excretion, however, was markedly increased. Inhibiting distal hydrogen ion secretion by inducing selective aldosterone deficiency failed to uncover a vasopressin-induced inhibition of proximal bicarbonate reabsorption that might have been masked by increased distal bicarbonate reabsorption. There was no significant change in GFR, renal plasma flow, or filtration fraction. The distribution of cortical renal blood flow (measured by the radioactive microsphere technique) shifted toward the inner cortex after vasopressin administration. Vasopressin, in pharmacologic doses, is a potent diuretic that most likely exerts this effect by directly inhibiting sodium reabsorption at a point in the nephron distal to the proximal tubule.

The plasma electrolyte composition and 24-hour urine electrolyte excretion were determined in fasting normal, K-deficient and protein and K-deficient rats following the administration of equal molar quantities of NaCl, KCl, NH4Cl and KHCO3. An attempt was made to relate any differences in the compositions of the plasma and urine to the levels of renal glutaminase and carbonic anhydrase activities, and, to the chemical compositions of the skeletal muscle and kidneys. Renal glutaminase and carbonic anhydrase activities were found increased in K-deficiency and reduced in protein and K-deficiency. Significant changes from corresponding control levels of renal glutaminase were found in normal and K-deficient animals only after the administration of NH4Cl (increased), and, after the administration of KHCO3 (reduced). The only outstanding change of the carbonic anhydrase activity of the kidneys from these animals was a reduction following NH4Cl administration. The doubly deficient rats showed a significant increase in renal glutaminase activity after NH4Cl administration; on the other hand, KCl administration resulted in a further reduction of the lowered renal carbonic anhydrase activity. The experimental results supported the contention that a relationship exists between urinary ammonia excretion and the level of renal glutaminase activity, while the transfer of H+ to the urine and the level of renal carbonic anhydrase activity could not be related. No clear relationship was found between the K excretion and/or K content of the kidneys and the urine total titratable acidity and ammonia excretion, and urine ph.

The influence of hydration, of elastic bandaging of the lower extremities and of adrenal cortical insufficiency upon the renal retention of water, sodium and chloride associated with upright posture was studied. With ‘moderate hydration,’ the excretion of both water and electrolytes diminished when the subjects changed from the supine to the sitting position. With ‘intense hydration’ only electrolyte excretion diminished when the subjects sat up. Compression of the superficial veins of the lower extremities with elastic bandages diminished the expected postural antidiuresis and antisaluresis. Patients with treated adrenal cortical insufficiency did not demonstrate any antidiuresis when the sitting position was assumed. Submitted on December 12, 1955

Studies were made on dogs to clarify the actions of pentobarbital anesthesia on renal function. The depression of renal function frequently observed when anesthesia is induced in animals hydrated with water or hypotonic saline solutions was confirmed. When the neurogenically and hormonally mediated components of the response to pentobarbital are respectively blocked by dihydrogenated ergot alkaloids and Pitressin infusion, pentobarbital anesthesia increases sodium excretion rather than decreasing it. Infusion of pentobarbital directly into the renal artery suggests that this natriuresis is caused by a toxic action of the anesthetic on the sodium reabsorptive process. Some inhibition of the glucose transport process has also been described.

The effects of arginine vasopressin, oxytocin and two synthetic analogues, arginine vasotocin (8-arginine oxytocin) and oxypressin (8-leucine vasopressin), on urinary electrolyte excretion were studied in conscious dogs. Arginine vasopressin, 0.25 mu/kg, evokes a consistent natriuretic response during water diuresis, while at low urine flows the natriuretic response is usually absent. Oxytocin, 6–7 mu/kg, produces consistent natriuresis only at low urine flows. In higher doses, however, both hormones produce natriuresis either during water diuresis or at low urine flows. When doses of equal antidiuretic activity are injected arginine vasotocin produces greater natriuresis than arginine vasopressin; in this respect, oxypressin is the least potent. The kaliuretic effects of these four peptides are inconsistent. These studies suggest that the 8-arginine of vasopressin is important to natriuretic activity. Substitution of isoleucine for 3-phenylalanine in the ring also increases natriuretic activity relative to antidiuretic activity. This implies that the oxytocin ring also contributes to the saluretic activity of neurohypophysial peptides.

Two groups of rats were fed equal quantities of an electrolyte-free diet which was supplemented with potassium by gavage. One group received aldosterone in sesame oil and the other the vehicle by daily injection. The excretion of potassium was not influenced by the administration of aldosterone. In addition, there was no effect on the filtration rate or tissue electrolyte composition.