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.     

Determination of trimethoprim and sulfamethoxazole (co-trimoxazole) in body fluids of man by means of high-performance liquid chromatography

A high-performance liquid chromatographic method for the determination of trimethoprim, sulfamethoxazole and its metabolite and a series of structurally related sulfonamides is described. The half-life time of elimination of sulfamethoxazole and its metabolite N₄-acetylsulfamethoxazole is 9 h for both compounds. The renal excretion rate of sulfamethoxazole depends strongly on the urinary pH. The renal excretion rate of the metabolite N₄-acetylsulfamethoxazole is not dependent on the urinary pH.     

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.     

Effects of triamcinolone and of desoxycorticosterone on renal function in sheep.

Sheep were treated for 10 or 17 days with triamcinolone acetonide, 0.1 mg/kg body weight/day, or desoxycorticosterone acetate, 0.1 mg/kg body weight/day, and the results of renal function studies during hydropenia and mannitol diuresis were compared with respective control periods. GFR was increased and urine concentration was unimpaired by treatment with triamcinolone. A consistent decrease in mannitol-induced Na excretion was observed, but with large variations in the mean change, in triamcinolone treatment periods. Treatment with desoxycorticosterone resulted in an increased GFR but with impaired urine concentrating capacity. The hypokalemia produced by desoxycorticosterone was not accompanied by an increase in urinary K excretion. During mannitol diuresis in sheep treated with desoxycorticosterone, there was a significant decrease in Na excretion when compared with control periods.     

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.     

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.     

Response of the Infant Kidney to Diuretic Drugs

The diuretic response of normal infants, 6 to 47 days of age, to single doses of mercaptomerin, chlorothiazide, acetazolamide, triamterene and spironolactone was studied by following urinary electrolytes, pH and osmolality. Peak diuresis occured two to four hours after drug administration, and because of compensatory mechanisms little change in urinary excretion was found if only 24-hour urines were studied. Mercaptomerin increased sodium excretion seven-fold, compared to three- to four-fold increases for the other diuretics. Control urinary Na:K ratios averaged 0.68 in infants compared to 2.8 for adults, and mercaptomerin produced the largest increase in this ratio. Qualitatively the response to diuretics is the same in newborn in the ages studied as it is reported to be for adults; no immaturity of the infant kidney in this regard was demonstrated.     

Low sodium intake does not impair renal compensation of hypoxia-induced respiratory alkalosis.

Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased diuresis and sodium, potassium, and bicarbonate excretion. With a low sodium intake, the excretion of the anion bicarbonate may be limited by the lower excretion rate of the cation sodium through activated sodium-retaining mechanisms. This study investigates whether the short-term renal compensation of hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium x kg body wt-1 x day-1) or high-sodium (HS = 7.5 mmol sodium x kg body wt-1 x day-1) diet. The dogs breathed spontaneously via a ventilator circuit during the experiments: first hour, normoxia (inspiratory oxygen fraction = 0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During hypoxia (arterial PO2 34.4 +/- 2.1 Torr), plasma pH increased from 7.37 +/- 0.01 to 7.48 +/- 0.01 (P < 0.05) because of hyperventilation (arterial PCO2 25.6 +/- 2.4 Torr). Urinary pH and urinary bicarbonate excretion increased irrespective of the sodium intake. Sodium excretion increased more during HS than during LS, whereas the increase in potassium excretion was comparable in both groups. Thus the quick onset of bicarbonate excretion within the first hour of hypoxia-induced respiratory alkalosis was not impaired by a low sodium intake. The increased sodium excretion during hypoxia seems to be combined with a decrease in plasma aldosterone and angiotensin II in LS as well as in HS dogs. Other factors, e.g., increased mean arterial blood pressure, minute ventilation, and renal blood flow, may have contributed.     

Electrolyte excretion in alcohol preferring and alcohol avoiding rats

Water and electrolyte metabolism was studied in alcohol preferring (AA) and alcohol avoiding (ANA) rats. During water diuresis AA rats had higher Mg, cAMP, creatinine and inorganic phosphate excretion, but lower urine and urinary protein output. During ethanol diuresis AA rats had lower Na, K, Ca, protein and urine output, but higher cAMP and inorganic phosphate excretion. Ethanol increased K, Ca and urine output in ANA rats only. A slight increase of blood pH was observed only in AA rats. Before ethanol ANA rats had higher plasma Ca concentration. Plasma aldosterone level was higher in AA rats. High salt excretion of ANA rats may lead them to prefer salt containing energy sources and therefore to avoid ethanol. On the other hand, renal salt conservation in AA rats may lead them to prefer ethanol.     

The effect of prostaglandin synthetase inhibitors on renal function: Studies in normal rats during sodium or water diuresis and in rats with chronic renal insufficiency

The effect of acute infusion of the prostaglandin synthetase inhibitors — meclofenamate or indomethacin — was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups. Absolute urinary excretion rates for sodium and potassium decreased only in the normal, salt-replete rats. In contrast, prostaglandin synthetase inhibitors consistently decreased urinary flow and osmolar clearance under all experimental conditions studied. In the normal, salt-replete rats the fall in urine flow was preceded by an increase in urinary excretion of cyclic AMP. These results show that inhibitors of prostaglandin synthesis enhance the ability of the kidney to reabsorb water. This effect may be secondary to increased cyclic AMP generation and to increased urea recirculation resulting in higher urea accumulation in the renal medulla.     

The effect of prostaglandin synthetase inhibitors on renal function: studies in normal rats during sodium or water diuresis and in rats with chronic renal insufficiency

The effect of acute infusion of the prostaglandin synthetase inhibitors - meclofenamate or indomethacin - was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups. Absolute urinary excretion rates for sodium and potassium decreased only in the normal, salt-replete rats. In contrast, prostaglandin synthetase inhibitors consistently decreased urinary flow and osmolar clearance under all experimental conditions studied. In the normal, salt-replete rats the fall in urine flow was preceded by an increase in urinary excretion of cyclic AMP. These results show that inhibitors of prostaglandin synthesis enhance the ability of the kidney to reabsorb water. This effect may be secondary to increased cyclic AMP generation and to increased urea recirculation resulting in higher urea accumulation in the renal medulla.     

垂体在刺激脑内渗透压感受器引起的肾脏反应中的作用

实验在α氯醛糖和氨基甲酸乙酯混合麻醉的大鼠中进行。脑室内注射高张盐水(icv.HS)后,肾血浆流量、肾小球滤过率、尿量、尿钠排出量、尿钾排出量和渗透物质清除率均增加,游离水清除率下降。去除垂体后,icv.HS不再能引起上述肾脏反应。另外给大鼠静脉注射血管升压素(VP)拮抗剂(V_1和V_2受体拮抗剂),并不能削弱上述icv.HS引起的肾脏反应。脑室内注射高张盐水后,尿中多巴胺(DA)排出量无显著增多;给予多巴脱羧酶抑制剂苄丝肼也不能削弱icv.HS引起的肾脏反应。上述实验结果表明,在本实验条件下刺激脑内渗透压感受器引起的肾脏反应依赖于垂体的完整性,但看来并不依赖于外周的VP和DA,故垂体通过何种机制介导icv.HS引起上述肾脏反应,有待于进一步的研究。     

The effects of two analogues of arginine-vasopressin (ornithine-vasopressin and desamino-D-arginine-vasopressin) on kidney function in sheep.

The effects of intravenous infusion of ornithine-vasopressin (OVP) and desamino-D-arginine-vasopressin (dDAVP) were studied in normal and hydrated Merino sheep. In normal sheep, OVP resulted in a diuresis, increased urinary sodium and potassium excretion, and a fall in the plasma potassium concentration. Renal plasma flow remained constant but glomerular filtration rate and filtration fraction rose markedly. dDAVP in normal sheep was antidiuretic, but its only significant effect was a small decrease in plasma osmolality. In the hydrated sheep OVP was antidiuretic and resulted in increased urinary excretion of sodium and potassium, and a fall in the plasma potassium level. Renal plasma flow fell, but glomerular filtration and filtration fraction tended to rise. dDAVP in the hydrated sheep was also antidiuretic but urinary sodium and potassium excretion was reduced. Renal plasma flow and glomerular filtration fell, with a small decrease in filtration fraction. These results suggest that the diuretic effect in normal sheep and the electrolyte-excreting effects in both normal and hydrated sheep of OVP are related to the increase in glomerular filtration, which in turn is dependent on the vasopressor activity of the hormone. The increase in glomerular filtration caused by OVP is due to an increase in the filtration fraction of an unchanged renal plasma flow, which could be brought about by an increase in renal efferent arteriolar tone. The effects of hydration of the sheep were the conventional increased urine flow, decreased urine osmolality and decreased solute-free water reabsorption. Sodium and potassium excretion rose slightly and plasma osmolality fell. Renal plasma flow and glomerular filtration both increased with little change in filtration fraction. These effects could be brought about by suppression of endogenous vasopressin and a decrease in both afferent and efferent renal arteriolar tone.     

Effect of somatostatin on renal water handling in the dog

When somatostatin was infused into the left renal artery of anaesthetized, hydropenic dogs in doses ranging from 1 to 10 micrograms/min, it produced an increased flow of a more dilute urine from the ipsilateral kidney. Similar infusions in dogs undergoing a maximal water diuresis had no effect. If aqueous antidiuretic hormone (ADH) was administered intravenously into water-loaded dogs prior to the intraarterial infusion of somatostatin, this latter peptide was able to produce an augmented flow of a more dilute urine from the ipsilateral kidney. If the left kidney was made to excrete a concentrated urine in the face of maximal water loading by restricting arterial perfusion, then the infusion of somatostatin had no effect on urinary dilution, though this peptide could increase water excretion in hydropenic dogs when the left kidney was similarly restricted as to arterial inflow. In dogs undergoing a water diuresis that were given cyclic AMP (4 mg/min) into the left renal artery, a decrease in ipsilateral water excretion was observed. The subsequent infusion of somatostatin produced no urinary dilution. We conclude that somatostatin increases renal water excretion by antagonizing the ADH effect on the renal tubule, and that this event probably occurs at a pre-cAMP site within the cell.     

Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion

It is well established that activation of endothelin B (ETB) receptor induces natriuresis and diuresis and thus reduces blood pressure. However, the site of action of ETB receptor is debatable. The present study was undertaken to address the role of renal medullary ETB receptor in renal excretory function. In volume-expanded Sprague-Dawley rats, infusion of the ETB antagonist A192621 at 0.5 mg/kg/hr to the renal medulla induced an immediate and significant reduction of urine flow rate that was 87.5% +/- 7.1%, 68% +/- 20%, and 58.3% +/- 15.5% of the control value at 10, 30, and 60 mins, respectively (n=5, P < 0.05 at each time point). Following intramedullary infusion of A192621, urinary sodium excretion remained unchanged during the first 20 mins but started to decline thereafter with a maximal effect at 60 mins. Changes in urinary excretion of potassium and chloride followed the same pattern of changes as for urinary sodium. In contrast, urinary osmolality gradually and significantly increased (control: 419 +/- 66; A192621 at 60 mins: 637 +/- 204 mOsm/kg H2O, P < 0.05). Over a 60-min period of intramedullary infusion of A192621, none of the hemodynamic parameters examined, including mean arterial pressure, renal blood flow, or medullary blood flow, were affected. These data suggest that: (i) intramedullary blockade of ETB receptor produces antidiuresis and antinatriuresis independently of hemodynamic changes, and (ii) the immediate response to intramedullary blockade of ETB receptor is the reduction of water excretion followed by the reduction of sodium excretion.     

Endogenous central kappa-opioid systems augment renal sympathetic nerve activity to maximally retain urinary sodium during hypotonic saline volume expansion

Intracerebroventricular injection of kappa-opioid agonists produces diuresis, antinatriuresis, and a concurrent increase in renal sympathetic nerve activity (RSNA). The present study examined whether endogenous central kappa-opioid systems contribute to the renal excretory responses produced by the stress of an acute hypotonic saline volume expansion (HSVE). Cardiovascular, renal excretory, and RSNA responses were measured during control, acute HSVE (5% body weight, 0.45 M saline over 30 min), and recovery (70 min) in conscious rats pretreated intracerebroventricularly with vehicle or the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI). In vehicle-pretreated rats, HSVE produced a marked increase in urine flow rate but only a low-magnitude and delayed natriuresis. RSNA was not significantly suppressed during the HSVE or recovery periods. In nor-BNI-treated rats, HSVE produced a pattern of diuresis similar to that observed in vehicle-treated rats. However, during the HSVE and recovery periods, RSNA was significantly decreased, and urinary sodium excretion increased in nor-BNI-treated animals. In other studies performed in chronic bilateral renal denervated rats, HSVE produced similar diuretic and blunted natriuretic responses in animals pretreated intracerebroventricularly with vehicle or nor-BNI. Thus removal of the renal nerves prevented nor-BNI from enhancing urinary sodium excretion during HSVE. These findings indicate that in conscious rats, endogenous central kappa-opioid systems are activated during hypotonic saline volume expansion to maximize urinary sodium retention by a renal sympathoexcitatory pathway that requires intact renal nerves.     

Long-Term Responses to Loss of Renal Mass: Pathophysiological Aspects: The Effects of Functional Adaptation of Residual Nephrons on the Urinary Excretion of Drugs

In patients with chronic renal failure due to glomerulonephritis, pyelonephritis or polycystic kidneys the urinary clearance of free chloramphenicol (C_CHL) was depressed proportionally to GFR (C_In). The ordinate intercept of the regression line of C_CHL on C_In, however, consistently was positive (+3 to +5 ml/min). The fractional excretion of chloramphenicol in renal failure increased from its normal value of 50 percent as an exponential function of the decrease of GFR, and as a linear function of the fractional excretion of water or of sodium. Dietary sodium restriction had no influence on C_CHL in the patients, while water diuresis, in normal subjects, enhanced the urinary excretion of chloramphenicol. The data suggest that chloramphenicol is reabsorbed by back-diffusion and that increases of the rate of flow of urine and tubular fluid prevent back-diffusion.     

Urinary excretion of prostaglandin E like material and kallikrein: Effects of furosemide

In a controlled study of 11 women, 5 with mild essential hypertension and 6 normal volunteers, furosemide produced a significant natriuresis and diuresis without changes in the urinary excretion of prostaglandin E-like material and kallikrein. Therefore, although some evidence in man or animals suggests involvement of both of these substances in renal responses to furosemide, the present data suggest that the natriuretic and diuretic effects of this drug are not associated with an increased excretion of prostaglandin E like material or kallikrein.     

Diuretic action of calcitonin: demonstration of an inhibiting effect on sodium reabsorption in the ascending limb of Henlé's loop]

It was found that calcitonin (porcine) at the dose: 4 I.U. MRC./kg/hr (i.v.), in the rabbit, increased the diuresis and oxmolal excretion, and simultaneously decreased free-water reabsorption and urinary osmolality. The results suggest that calcitonin acts by inhibiting sodium reabsorption in the ascending limb of Henl's loop. This hypothesis was confirmed by renal autoradiography study with 22Na.     

Effect of increased diuresis on the renal excretion of sulfamerazine]

The excretion velocity of sulfamerazine is very slow, caused by a high reabsortion rate in renal tubuli. An increased diuresis by i.p. administration of saline or p.o. load with water has no effect on the sulfamerazine excretion velocity. The enhanced diuresis is accompanied by a decrease of the urine pH-value and consequently by a decreased dissociation rate of sulfamerazine.