Nephron site of effect of nonsteroidal anti-inflammatory drugs on solute excretion in humans

1983 ◽  
Vol 244 (2) ◽  
pp. F134-F139 ◽  
Author(s):  
S. Kaojarern ◽  
P. Chennavasin ◽  
S. Anderson ◽  
D. C. Brater
Keyword(s):  
Free Water ◽  
Fractional Excretion ◽  
Thick Ascending Limb ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Water Loading ◽  
Fractional Excretion Of Sodium ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Solute Excretion

Indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) decrease solute excretion when administered acutely to normal subjects. We performed clearance studies during water loading of 10 normal volunteers and during hydropenia in eight additional subjects to determine the nephron site of this effect using indomethacin and carprofen as inhibitors of prostaglandin (PG) synthesis. Their administration decreased fractional excretion of sodium, chloride, and volume. During water loading, fractional clearance of free water decreased from 0.13 +/- 0.04 during the control study to 0.09 +/- 0.03 and 0.06 +/- 0.02 with indomethacin and carprofen, respectively. However, fractional delivery of solute to the dilution segment decreased in parallel such that free water clearance corrected for delivery did not change with either drug. In humans, therefore, the decrement in solute excretion that occurs with administration of NSAIDs occurs prior to the diluting segment. During hydropenia, free water reabsorption relative to osmolar clearance increased (P less than 0.01). In both studies, neither the marker of renal perfusion or of proximal nephron function changed with inhibition of PG synthesis. The data indicate that at the tubular level, NSAIDs increase solute reabsorption at the medullary segment of the thick ascending limb of the loop of Henle. Therefore, a physiologic role of renal prostaglandins at this nephron site is implied.

Characterization of the Natriuresis Caused in Normal Man by Immersion in Water

1972 ◽  
Vol 43 (2) ◽  
pp. 275-287 ◽  
Author(s):  
M. Epstein ◽  
D. C. Duncan ◽  
L. M. Fishman
Keyword(s):  
Water Immersion ◽  
Control Period ◽  
Free Water ◽  
Fractional Excretion ◽  
Normal Male ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Sodium Load ◽  
Proximal Tubular ◽  
Normal Man

1. The effects of 4–6 h of water immersion on the renal excretion of water and electrolytes were studied in thirteen normal male subjects in balance on a constant diet containing 150 mEq of Na and 100 mEq of K per day. Each subject was studied during a control period, consisting of quiet sitting, and during water immersion to the neck. 2. Immersion resulted in a natriuresis beginning within the first hour, with the rate of sodium excretion eventually exceeding that of the control period by 3–4-fold; potassium excretion also increased. Despite a progressively negative water balance during the immersion studies, urine flow was greater during the first 4 h and free water clearance was greater during the first 2 h of immersion than during the control study. 3. The demonstration of a highly significant increase in fractional excretion of sodium during immersion suggests that the natriuresis of water immersion is not attributable to changes in filtered sodium load. 4. The prompt onset of the natriuresis, the concomitant kaliuresis and the fact that aldosterone secretion under the conditions of study was probably already suppressed make it unlikely that the natriuresis of water immersion is mediated solely by decreases in aldosterone activity. 5. The data suggest that the natriuresis caused by water immersion is the result of decreased fractional reabsorption of sodium proximal to the renal diluting site. The mechanism whereby increased proximal tubular sodium rejection occurs in relation to immersion remains unclear.

scholarly journals Pentavalent antimonial nephrotoxicity in the rat

1990 ◽  
Vol 32 (4) ◽  
pp. 304-309 ◽  
Author(s):  
Joel Paulo R. Veiga ◽  
Rashida Khanam ◽  
Tânia T. Rosa ◽  
Luiz F. Junqueira Jr. ◽  
Plínio C. Brant ◽  
...  
Keyword(s):  
Free Water ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
High Dose ◽  
Urinary Flow ◽  
Free Water Clearance ◽  
Functional Changes ◽  
Histopathological Alterations ◽  
Fractional Excretion Of Sodium

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sb v (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Effect of Prolactin on Glomerular Filtration Rate

1978 ◽  
Vol 55 (4) ◽  
pp. 335-339 ◽  
Author(s):  
A. L. Riley ◽  
T. C. Hagen ◽  
J. E. Stefaniak
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Free Water ◽  
Flow Distribution ◽  
Fractional Excretion ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Ovine Prolactin

1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin. 2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12–18% increase in glomerular filtration rate (GFR) by both kidneys. 3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance. 4. We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow.

scholarly journals Defective renal water handling in transgenic mice over-expressing human CD39/NTPDase1

2012 ◽  
Vol 303 (3) ◽  
pp. F420-F430 ◽  
Author(s):  
Yue Zhang ◽  
Kaiya L. Morris ◽  
Shannon K. Sparrow ◽  
Karen M. Dwyer ◽  
Keiichi Enjyoji ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Free Water ◽  
Fractional Excretion ◽  
Urinary Concentration ◽  
Free Water Clearance ◽  
Water Handling ◽  
Fractional Excretion Of Sodium ◽  
Urinary Concentrating Ability

Ectonucleoside triphosphate diphosphohydrolase-1 hydrolyzes extracellular ATP and ADP to AMP. Previously, we showed that CD39 is expressed at several sites within the kidney and thus may impact the availability of type 2 purinergic receptor (P2-R) ligands. Because P2-Rs appear to regulate urinary concentrating ability, we have evaluated renal water handling in transgenic mice (TG) globally overexpressing hCD39. Under basal conditions, TG mice exhibited significantly impaired urinary concentration and decreased protein abundance of AQP2 in the kidney compared with wild-type (WT) mice. Urinary excretion of total nitrates/nitrites was significantly higher in TG mice, but the excretion of AVP or PGE2 was equivalent to control WT mice. There were no significant differences in electrolyte-free water clearance or fractional excretion of sodium. Under stable hydrated conditions (gelled diet feeding), the differences between the WT and TG mice were negated, but the decrease in urine osmolality persisted. When water deprived, TG mice failed to adequately concentrate urine and exhibited impaired AVP responses. However, the increases in urinary osmolalities in response to subacute dDAVP or chronic AVP treatment were similar in TG and WT mice. These observations suggest that TG mice have impaired urinary concentrating ability despite normal AVP levels. We also note impaired AVP release in response to water deprivation but that TG kidneys are responsive to exogenous dDAVP or AVP. We infer that heightened nucleotide scavenging by increased levels of CD39 altered the release of endogenous AVP in response to dehydration. We propose that ectonucleotidases and modulated purinergic signaling impact urinary concentration and indicate potential utility of targeted therapy for the treatment of water balance disorders.

Dysfunction of the proximal tubule underlies maleic acid-induced type II renal tubular acidosis

1982 ◽  
Vol 243 (6) ◽  
pp. F604-F611 ◽  
Author(s):  
H. A. Al-Bander ◽  
R. A. Weiss ◽  
M. H. Humphreys ◽  
R. C. Morris
Keyword(s):  
Proximal Tubule ◽  
Renal Tubular Acidosis ◽  
Maleic Acid ◽  
Free Water ◽  
Fractional Excretion ◽  
Thick Ascending Limb ◽  
Type Ii ◽  
Free Water Clearance ◽  
Plasma Bicarbonate ◽  
Renal Tubular

To investigate whether dysfunction of the proximal tubule underlies maleic acid-(MA) induced type II (“proximal”) renal tubular acidosis (RTA II), we intravenously administered either MA or acetazolamide to eight conscious trained dogs undergoing water diuresis and examined the relationship between fractional solute-free water clearance (Ch2o/GFR), a measure of NaCl reabsorption in the post-proximal nephron, and either fractional urine flow (V/GFR), a measure of total solute rejected by the proximal tubule, or the sum of fractional excretion of Cl- and Ch2o/GFR [(Ccl + Ch2o)/GFR], a measure of proximally rejected solute that is potentially reabsorbable by the thick ascending limb. When MA or acetazolamide induced brisk bicarbonaturia at normal plasma bicarbonate concentrations: 1) V/GFR, (Ccl + Ch20)GFR, and Ch2o/GFR increased strikingly; 2) at any increment of Ch2o/GFR ws not; 3) the increments of V/GFR correlated positively with those of fractional excretion of bicarbonate (P less than 0.001); 4) during hyperchloremic acidosis, MA-induced bicarbonaturia was greatly attenuated; the increment in V/GFR was halved and approximated that in Ch20/GFR, which was unchanged; 5) when plasma bicarbonate was abruptly increased, bicarbonaturia increased strikingly and V/GFR increased further but Ch20/GFR and aminoaciduria did not. We conclude that MA induces a reduction in the net rate at which the proximal tubule reabsorbs HCO-3, Na+, and Cl-. This dysfunction underlies RTA II and evokes greatly increased reabsorption of Cl- and Na+ in the post-proximal tubule.

Effects of indomethacin on renal response to atrial natriuretic peptide

1987 ◽  
Vol 253 (5) ◽  
pp. F868-F873
Author(s):  
C. A. Gaillard ◽  
H. A. Koomans ◽  
A. J. Rabelink ◽  
E. J. Mees
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Free Water ◽  
Fractional Excretion ◽  
Lithium Clearance ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
Water Clearance

We studied the effect of alpha-human natriuretic peptide (ANP, 100 micrograms iv) on renal sodium handling in eight healthy subjects before and after 7 days of indomethacin (50 mg 3 times a day). Sodium intake was 100 mmol/day. Prior to indomethacin, ANP caused a fourfold rise in sodium excretion over the first 20 min and a threefold rise in fractional sodium excretion. The clearance studies, performed during maximal water diuresis, showed increased fractional free water clearance and lithium clearance. Indomethacin caused marked sodium retention. Complete escape did not occur until the sixth day, when cumulative balance was 244 mmol (range 176-337). By this time renin and aldosterone were suppressed and fractional lithium and free water clearance reduced. The natriuretic effect of ANP was not attenuated, and the fractional excretion of sodium and chloride rose even more than without indomethacin. The reduction in lithium and free water clearance under indomethacin tended to be reversed by ANP. These data suggest that the natriuretic effect of ANP is not mediated by or dependent on renal prostaglandins. Indomethacin and ANP appear to have opposite effects on sodium excretion, maximal free water clearance, and lithium clearance.

Estrogen effects on osmotic regulation of AVP and fluid balance

2002 ◽  
Vol 283 (4) ◽  
pp. E711-E721 ◽  
Author(s):  
Nina S. Stachenfeld ◽  
David L. Keefe
Keyword(s):  
Free Water ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Hormone Treatment ◽  
Osmotic Regulation ◽  
Gnrh Analog ◽  
Free Water Clearance ◽  
Fractional Excretion Of Sodium ◽  
Endogenous Estrogen ◽  
Estrogen Effects

To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP) and body fluids, we suppressed endogenous estrogen and progesterone using the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n = 9, 25 ± 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n = 6, 26 ± 3). During GnRHa alone and with hormone treatment, we compared AVP and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml · min−1 · kg body wt−1), drinking (30 min, 15 ml/kg body wt), and recovery (60 min of seated rest). Plasma [E2] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P4] increased from 0.6 to 5.7 ng/ml during E/P and was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced osmotic AVP release threshold (275 ± 4 to 271 ± 4 mosmol/kg, P < 0.05), and E/P reduced the AVP increase in response during HSI (6.0 ± 1.3 to 4.2 ± 0.6 pg/ml at the end of HSI), but free water clearance was unaffected in either group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during E (0.8 ± 0.1 vs. 1.2 ± 0.2 ng ANG I · ml−1 · h−1) but not after HSI or recovery. PRA was greater than GnRHa during E/P at baseline (1.1 ± 0.2 vs. 2.5 ± 0.6) and after HSI (0.6 ± 0.1 vs. 1.1 ± 1.1) and recovery (0.5 ± 0.1 vs. 1.3 ± 0.2 ng ANG I · ml−1 · h−1). Baseline fractional excretion of sodium was unaffected by E or E/P but was attenuated by the end of recovery for both E (3.3 ± 0.6 vs. 2.4 ± 0.4%) and E/P (2.8 ± 0.4 vs 1.7 ± 0.4%, GnRHa alone and with hormone treatment, respectively). Fluid retention increased with both hormone treatments. Renal sensitivity to AVP may be lower during E due to intrarenal effects on water and sodium excretion. E/P increased sodium retention and renin-angiotensin-aldosterone stimulation.

The Actions of Bradykinin and Eledoisin in the Canine Isolated Kidney: Relationships to Prostaglandins

1975 ◽  
Vol 49 (2) ◽  
pp. 125-131 ◽  
Author(s):  
J. C. McGiff ◽  
H. D. Itskovitz ◽  
N. A. Terragno
Keyword(s):  
Filtration Rate ◽  
Free Water ◽  
Fractional Excretion ◽  
Prostaglandin Synthesis ◽  
Isolated Kidney ◽  
Free Water Clearance ◽  
Urinary Osmolality ◽  
Fractional Excretion Of Sodium ◽  
Before And After ◽  
Vasodilator Action

1. The effects of two vasodilator polypeptides, bradykinin and eledoisin, were studied in isolated blood-perfused canine kidneys before and after administration of indomethacin, an inhibitor of prostaglandin synthesis. Bradykinin, but not eledoisin, releases renal prostaglandins. 2. Before administration of indomethacin, bradykinin decreased urinary osmolality and increased free water clearance, whereas eledoisin did not affect the excretion of solute-free water. After administration of indomethacin, the renal vasodilator action of bradykinin was reduced but the vasodilator action of eledoisin was unaffected. 3. Fractional excretion of sodium was not affected by bradykinin before but was increased after administration of indomethacin. Reduction in glomerular filtration rate contributed to changes in sodium excretion produced by bradykinin and eledoisin. 4. The release of prostaglandins from the kidney by bradykinin amplifies the renal vasodilator action of the kinin and possibly mediates its effect on excretion of solute-free water.

Lithium clearance in water immersion-induced natriuresis in humans

1989 ◽  
Vol 66 (4) ◽  
pp. 1744-1748 ◽  
Author(s):  
T. J. Rabelink ◽  
H. A. Koomans ◽  
W. H. Boer ◽  
J. van Rijn ◽  
E. J. Dorhout Mees
Keyword(s):  
Healthy Subjects ◽  
Water Immersion ◽  
Free Water ◽  
Fractional Excretion ◽  
Lithium Clearance ◽  
Free Water Clearance ◽  
Time Control ◽  
Fractional Excretion Of Phosphate ◽  
Response To Water ◽  
Glomerulotubular Balance

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of renal function of rats following spaceflight

1998 ◽  
Vol 275 (4) ◽  
pp. R1058-R1065 ◽  
Author(s):  
Charles E. Wade ◽  
Emily Morey-Holton
Keyword(s):  
Renal Function ◽  
Excretion Rate ◽  
Free Water ◽  
Male Rats ◽  
Free Water Clearance ◽  
Creatinine Excretion ◽  
Flight Controls ◽  
Excretion Rates ◽  
Solute Excretion ◽  
Water Clearance

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats (∼245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals ( n = 6), flight controls ( n = 6) housed in the flight cages on the ground, and vivarium controls ( n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

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