Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans

2002 ◽  
Vol 103 (5) ◽  
pp. 461-466 ◽  
Author(s):  
D.G. SHIRLEY ◽  
S.J. WALTER ◽  
F.H. NOORMOHAMED
Keyword(s):  
Control Period ◽  
Fractional Excretion ◽  
Experimental Period ◽  
Caffeine Intake ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Distal Nephron ◽  
Clearance Ratio ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect

In order to assess the intrarenal mechanisms responsible for the natriuretic action of caffeine, the renal clearances of 51Cr-EDTA [used as a measure of glomerular filtration rate (GFR)] and lithium (used as an index of end-proximal fluid delivery) were measured in eight healthy males before (control period) and immediately after (experimental period) a 400mg oral dose of caffeine (given over 90min) or placebo. In caffeine-treated subjects, the fractional excretion of sodium rose from 1.00±0.25% in the control period to 1.47±0.18% in the experimental period, while corresponding values on the placebo day were 1.04±0.16% and 0.70±0.07% respectively. GFR was unchanged following either caffeine or placebo. When compared with the placebo day, caffeine caused increases in lithium clearance (experimental period values: caffeine, 37±1ml/min; placebo, 28±2ml/min; P<0.001), the fractional excretion of lithium (caffeine, 34±1%; placebo, 26±2%; P<0.001) and the sodium/lithium clearance ratio (used as an index of the fraction of sodium delivered to the distal nephron that escapes reabsorption therein: caffeine, 4.4±0.3%; placebo, 2.8±0.2%; P<0.001). These results suggest that reduced fractional sodium reabsorption in both the proximal tubule and the distal nephron contributes to the acute natriuretic effect of caffeine. The data also confirm the importance of controlling caffeine intake when investigating renal function using lithium clearance.

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.

Cimetidine administration and tubular creatinine secretion in patients with compensated cirrhosis

2001 ◽  
Vol 102 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Giovanni SANSOÈ ◽  
Alberto FERRARI ◽  
Carmen Nives CASTELLANA ◽  
Lorenzo BONARDI ◽  
Erica VILLA ◽  
...  
Keyword(s):  
Oral Administration ◽  
Fractional Excretion ◽  
Tubular Secretion ◽  
Inulin Clearance ◽  
Sodium Reabsorption ◽  
Lithium Clearance ◽  
Clearance Ratio ◽  
Compensated Cirrhosis ◽  
Tubular Sodium Reabsorption ◽  
Sodium Load

Cimetidine inhibits the tubular secretion of creatinine, without altering the glomerular filtration rate (GFR). During cimetidine administration the creatinine/inulin clearance ratio approaches unity in patients with renal failure. We determined the clearance of lithium (an index of fluid delivery to the distal nephron), inulin (a measure of the actual GFR) and creatinine during cimetidine administration to investigate the occurrence of tubular creatinine secretion in patients with compensated cirrhosis. A total of 12 patients with Child-Pugh A cirrhosis were studied initially. The subjects consumed a stable diet containing 100mmol of sodium. On successive days, 9h creatinine clearances were measured, first without and then with the oral administration of cimetidine (400mg as a priming dose, followed by 200mg every 3h). During the first study day, 4h renal lithium clearance was also calculated. A further group of five patients with fully compensated cirrhosis underwent the measurement (on successive days) of plasma inulin clearance, first without and then with the oral administration of cimetidine (same schedule of drug administration). Cimetidine administration unmasked a marked overestimation of GFR when calculated as creatinine clearance (baseline, 138±20ml/min; +cimetidine, 89±13ml/min; P < 0.01). Consequently, during cimetidine administration the calculated lithium fractional excretion (a measure of the fraction of filtered sodium load that is delivered to the loop of Henle) rose from 21.4±13.2% to 32.3±18.9% (P < 0.05), and the ratio between absolute distal tubular sodium reabsorption and filtered sodium load rose from 20.6±13.1% to 31.6±19.3% (P < 0.01). Cimetidine caused no significant decrease in the actual GFR (i.e. inulin clearance) when administered to the second group of patients with compensated cirrhosis. Our data demonstrate significant tubular secretion of creatinine in patients with compensated cirrhosis and, consequently, a marked overestimation of GFR and filtered sodium load and an underestimation of the fractional distal tubular sodium reabsorption when these parameters are calculated by means of the traditional creatinine and lithium clearance computation. The true GFR (measured as inulin clearance) is unaffected by cimetidine administration.

Decreased distal acidification in acute hypercapnia in the dog

1983 ◽  
Vol 244 (1) ◽  
pp. F19-F27
Author(s):  
H. J. Adrogue ◽  
B. J. Stinebaugh ◽  
A. Gougoux ◽  
G. Lemieux ◽  
P. Vinay ◽  
...  
Keyword(s):  
Extracellular Fluid ◽  
Respiratory Acidosis ◽  
Fractional Excretion ◽  
Distal Nephron ◽  
Sodium Potassium ◽  
Fractional Excretion Of Sodium ◽  
Dependent Component ◽  
Voltage Dependent ◽  
Bicarbonate Infusion

The present studies evaluate the effect of acute hypercapnia on distal nephron H+ secretion (DNH+S) in vivo by means of the urine-blood PCO2 difference (U-B PCO2) in alkaline urine. Bicarbonaturia was induced by either a sodium bicarbonate infusion or L-lysine administration. Our results demonstrate that the U-B PCO2, as a function of the urinary bicarbonate concentration, was significantly lower during acute respiratory acidosis; this effect was not dependent on changes in glomerular filtration rate and/or fractional excretion of sodium, potassium, and chloride. Infusion of the sodium salts of sulfate, a nonreabsorbable anion, did not correct the diminished U-B PCO2. Amiloride caused the U-B PCO2 to fall in normocapnic dogs but not in hypercapnic dogs. When hypercapnia was superimposed in dogs with extracellular fluid volume contraction, there were no changes in the U-B PCO2. This study indicates that acute hypercapnia in the intact dog decreases DNH+S and is compatible with an effect of hypercapnia on the voltage-dependent component of urine acidification. The mechanism appears to be direct rather than secondary to factors that influence the rate of sodium delivery to the distal nephron.

Effect of Phlorhizin on Renal Glucose and Phosphate Transport in the Dog

1979 ◽  
Vol 57 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Sung-Feng Wen
Keyword(s):  
Proximal Tubule ◽  
Sodium Transport ◽  
Fractional Excretion ◽  
Phosphate Transport ◽  
Reciprocal Relationship ◽  
Sodium Reabsorption ◽  
Group I ◽  
Glucose Reabsorption ◽  
Fractional Excretion Of Sodium ◽  
Proximal Tubular

1. Clearance and micropuncture studies were performed in 19 thyroparathyroidectomized dogs to examine the inter-relationship between the renal transport of sodium, glucose and phosphate. 2. All experiments were carried out before and after the intravenous administration of phlorhizin [7 mg (15 μmol)/kg] with a sustaining infusion of the same dose/h. Thirteen dogs were studied during hydropenia (group I) and six dogs in the volume-expanded state (group II). 3. In the proximal tubule, phlorhizin significantly reduced sodium reabsorption in hydropenic dogs, but had no effect in volume-expanded dogs. Proximal tubular glucose reabsorption was completely inhibited by phlorhizin in both groups, but no significant change in phosphate reabsorption was observed. 4. Fractional glucose excretion in the urine reached 83–89% after phlorhizin, values significantly less than 100%, suggesting a residual reabsorption of glucose in a more distal segment or in deep nephrons. The changes in fractional excretion of sodium and phosphate were significantly correlated. 5. The effect of phlorhizin on both sodium and glucose reabsorption in the proximal tubule in hydropenic dogs suggests the existence of a co-transport mechanism, whereas the absence of an effect on sodium transport in volume-expanded dogs despite complete inhibition of glucose reabsorption indicates the existence of a sodium-independent component of net proximal tubular glucose transport. 6. Absence of the effect of phlorhizin on proximal tubular phosphate transport in the face of a significant reduction in sodium reabsorption implies that the reciprocal relationship between glucose and phosphate transport could be masked by the changes in sodium transport. Thus the sodium-phosphate transport relationship may prevail over that of glucose-phosphate in the proximal tubule.

scholarly journals Interactions between nitric oxide and renal nerves on pressure-diuresis and natriuresis.

1998 ◽  
Vol 9 (9) ◽  
pp. 1588-1595
Author(s):  
M I Madrid ◽  
M G Salom ◽  
J Tornel ◽  
E López ◽  
F J Fenoy
Keyword(s):  
Nitric Oxide ◽  
Renal Denervation ◽  
Fractional Excretion ◽  
Renal Nerves ◽  
High Dose ◽  
Lower Baseline ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
High Doses ◽  
Pressure Natriuresis

The present study examined the effect of renal denervation on the impairment of the pressure-diuresis response produced by nitric oxide synthesis blockade. The experiments were performed in Inactin-anesthetized Munich-Wistar rats. The animals with innervated kidneys had lower baseline values of renal blood flow, GFR, sodium excretion (UNaV), and urine flow (V) than rats with denervated kidneys. Also, renal denervation shifted pressure-diuresis and natriuresis toward lower pressures. A low dose of N(omega)-nitro-L-arginine methyl esther (NAME, 3.7 nmol/kg per min) reduced UNaV and the fractional excretion of sodium (FENa) and blunted pressure-natriuresis only in rats with innervated kidneys, whereas it had no effects in rats with denervated kidneys. A medium dose of NAME (37 nmol/kg per min) lowered FENa only in rats with innervated kidneys. The administration of NAME (37 nmol/kg per min) blunted pressure-diuresis and natriuresis in kidneys with or without the renal nerves, but the effect was more pronounced in rats with innervated kidneys. A high dose of NAME (3.7 micromol + 185 nmol/kg per min) increased UNaV and FENa only in rats with innervated kidneys, whereas it reduced GFR, V, UnaV, and FENa in rats with denervated kidneys. However, pressure-natriuresis and diuresis were blunted by this high dose of NAME independently of the presence or absence of renal nerves. These results demonstrate that renal nerves potentiate the renal effects of low doses of NAME on renal function and pressure-diuresis and natriuresis. However, high doses of NAME abolish pressure-diuresis independently of renal nerves, and the natriuretic effect of NAME in innervated kidneys may be attributed to reflex inhibition of sympathetic tone due to the rise in arterial pressure.

Role of nitric oxide in the natriuretic and diuretic responses in pregnant rats

2003 ◽  
Vol 285 (5) ◽  
pp. F938-F944 ◽  
Author(s):  
Ali A. Khraibi ◽  
Tianzheng Yu ◽  
Daiyi Tang
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sd Rats ◽  
Fractional Excretion Of Sodium ◽  
Lower Ability

Normal pregnancy is characterized by sodium conservation and increase in plasma volume, yet the natriuretic response to acute saline volume expansion (VE) is intact in pregnant rats. Nitric oxide (NO) has been suggested to play a role in renal and cardiovascular adaptations to normal pregnancy. The objective of this study was to determine the role of NO in the natriuretic and diuretic responses to VE during pregnancy. Infusion of NG-monomethyl-l-arginine (l-NMMA) was used to inhibit NO synthesis. Nine groups of Sprague-Dawley (SD) rats were studied: nonpregnant (NP-VE, n = 7), midterm pregnant (MP-VE, n = 8), and late-term pregnant (LP-VE, n = 7) SD groups that underwent VE alone after a control period; NP-l-NMMA ( n = 7), MP-l-NMMA ( n = 8), and LP-l-NMMA ( n = 7) SD groups that were infused with l-NMMA after a control period; and another three groups of SD rats (NP-VE-l-NMMA, n = 8; MP-VE-l-NMMA, n = 7; and LP-VE-l-NMMA, n = 12) that underwent simultaneous VE and l-NMMA infusion after a control period. The change in fractional excretion of sodium was 7.22 ± 1.03% for NPVE, 9.89 ± 1.85% for NP-l-NMMA, and 17.66 ± 1.85% for NP-VE-l-NMMA ( P < 0.05 vs. NP-VE and NP-l-NMMA); 6.61 ± 1.07% for MP-VE, 7.99 ± 1.92% for MP-l-NMMA, and 10.24 ± 1.91% for MP-VE-l-NMMA [not significant (NS) vs. MP-VE and MP-l-NMMA]; 8.20 ± 1.92% for LP-VE, 8.09 ± 0.70% for LP-l-NMMA, and 7.57 ± 1.11% for LP-VE-l-NMMA (both NS vs. LP-VE and LP-l-NMMA). The increase in renal interstitial hydrostatic pressure was significantly greater in all NP compared with pregnant groups with similar experimental intervention (i.e., VE, l-NMMA, or VE-l-NMMA). In conclusion, the natriuretic and diuretic responses to VE and l-NMMA infusion were additive in NP but not in pregnant rats, indicating a possible lower ability of pregnant rats to respond to combined significant natriuretic and diuretic stimuli.

Role of renal interstitial hydrostatic pressure in natriuretic response to ANP

1990 ◽  
Vol 258 (6) ◽  
pp. R1333-R1339 ◽  
Author(s):  
J. Garcia-Estan ◽  
R. J. Roman
Keyword(s):  
Hydrostatic Pressure ◽  
Renal Cortex ◽  
Collecting Duct ◽  
Fractional Excretion ◽  
Interstitial Pressure ◽  
Sodium Potassium ◽  
Fractional Excretion Of Sodium ◽  
Natriuretic Effect ◽  
Distal Delivery

The present study evaluated the role of changes in renal interstitial hydrostatic pressure (RIHP) in the natriuretic response to atriopeptin III (AP III). In control animals, infusion of AP III (100 ng.kg-1.min-1 iv) increased fractional excretion of sodium, potassium, lithium, and water while glomerular filtration rate and renal blood flow were unaltered. The natriuretic response to AP III was associated with a significant elevation in RIHP from 5.6 +/- 0.8 to 8.1 +/- 1.0 mmHg. In rats pretreated with amiloride (1 mg/kg) to block sodium transport in the collecting duct, basal sodium excretion was elevated, but infusion of AP III still increased RIHP and the fractional excretion of sodium, water, and lithium by the same amount as was observed in the control animals. Removal of the renal capsule completely blocked the rise in interstitial pressure in the renal cortex in amiloride-treated rats, but it did not eliminate the elevation in sodium, water, and lithium excretion produced by AP III. To determine whether changes in renal medullary interstitial pressure could play a role in the residual natriuretic response to AP III in these animals, cortical and medullary interstitial pressure were simultaneously measured in rats with a decapsulated kidney. In this group, AP III increased renal medullary interstitial pressure, while cortical interstitial pressure was unaltered. These results are consistent with the view that changes in renal medullary hemodynamics and RIHP contribute to the natriuretic effect of atrial natriuretic peptide by elevating distal delivery of sodium from deep nephrons.

Unimpaired excretion of an acute salt load in conscious hypoproteinaemic dogs

1988 ◽  
Vol 75 (3) ◽  
pp. 271-276 ◽  
Author(s):  
J. A. Joles ◽  
H. A. Koomans ◽  
P. Boer ◽  
E. J. Dorhout Mees
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Protein ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Isotonic Saline ◽  
Fractional Excretion ◽  
Sodium Reabsorption ◽  
Filtration Fraction ◽  
Fractional Excretion Of Sodium

1. The role of hypoproteinaemia in the sodium retention seen in conditions such as the nephrotic syndrome is incompletely known. 2. To define the influence of severe hypoproteinaemia on kidney function, we studied the effect of an intravenous infusion of an isotonic saline load (133 mmol of sodium), as 1 litre of Ringer lactate solution, on sodium excretion and renal haemodynamics in conscious dogs before and after reduction of plasma protein from 68 ± 3 to 36 ±2 g/l by repeated plasmapheresis and a low protein diet. 3. During hypoproteinaemia, 2 days after a period of plasmapheresis, glomerular filtration rate and effective renal plasma flow were lower than in the control study. After the sodium load, both rose to values nearly identical with the pre-infusion levels found in normoproteinaemia, the filtration fraction remaining unchanged. This contrasted with the rise in filtration fraction after expansion in normoproteinaemia, where filtration fraction increased from 32 to 39% due to a rise in glomerular filtration rate. 4. After expansion, natriuresis rose to similar levels in normoproteinaemia (0.18 ±0.06 mmol/min) and hypoproteinaemia (0.20 ± 0.06 mmol/min), and increments in fractional excretion of sodium, potassium and chloride were also similar. However, baseline excretion was higher in the hypoproteinaemic dogs due to their overhydrated condition in this period immediately after plasmapheresis. 5. The fractional excretion of lithium, an alleged marker of proximal tubular sodium reabsorption, rose to comparable levels. 6. Hence, both the increase in filtration and decrease in reabsorption of sodium after an isotonic saline load are not affected by severe reduction in plasma protein concentration. Apparently, the pathways to augment natriuresis after acute expansion function normally in hypoproteinaemia.

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.

Effect of Inhibition of Prostaglandin Synthesis on the Natriuresis Induced by Saline Infusion in Man

1978 ◽  
Vol 54 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Th. Mountokalakis ◽  
Th. Karambasis ◽  
D. Mayopoulousymvoulidou ◽  
G. Merikas
Keyword(s):  
Free Water ◽  
Prostaglandin Synthesis ◽  
Saline Infusion ◽  
Sodium Reabsorption ◽  
Distal Nephron ◽  
Prostaglandin Synthetase ◽  
Water Reabsorption ◽  
Post Infusion ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Natriuretic Effect

1. The effect of oral administration of an inhibitor of prostaglandin synthetase, indomethacin, on the natriuresis induced by the infusion of sodium chloride (saline) was studied in 11 healthy volunteers. 2. The administration of indomethacin did not alter sodium excretion before saline infusion, but it resulted in a significant increase of the natriuresis after saline infusion. This increase was not accompanied by any change in post-infusion urine flow rate or free water reabsorption. 3. It is suggested that intrarenal prostaglandins might suppress the natriuretic effect of saline infusion, probably by increasing sodium reabsorption in the distal nephron.

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