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.

Potentiation of the natriuretic effect of clonidine following indomethacin in the rat

1991 ◽  
Vol 69 (8) ◽  
pp. 1196-1203 ◽  
Author(s):  
Dorothea E. Blandford ◽  
Donald D. Smyth
Keyword(s):  
Sodium Excretion ◽  
Infusion Rate ◽  
Urine Volume ◽  
Free Water ◽  
Vehicle Group ◽  
Prostaglandin E ◽  
Free Water Clearance ◽  
Prostaglandin Production ◽  
Natriuretic Effect ◽  
Water Clearance

Previous studies have demonstrated a diuretic effect of clonidine at low intrarenal infusion rates with a natriuretic effect being observed at high infusion rates (≥3 μg∙kg−1∙min−1). The natriuresis at high infusion rates may have been secondary to increased renal prostaglandin production. We therefore evaluated the effects of indomethacin (a cyclooxygenase inhibitor) on the response to cionidine in the anesthetized rat. Intrarenal infusions of saline (vehicle) or clonidine (0.1, 0.3, 1, and 3 μg∙kg−1∙min−1) were examined both in the presence and absence of pretreatment with indomethacin (5 mg/kg, i.p.). Clonidine produced a dose-related increase in urine volume and free water clearance at 0.3, 1, and 3 μg∙kg−1∙min−1 as compared with the vehicle group. Sodium excretion and osmolar excretion were increased only at the highest infusion rate investigated. Following indomethacin pretreatment, clonidine produced a greater increase in urine volume at each infusion rate investigated. The indomethacin pretreatment also resulted in a potentiation of the natriuretic effect of clonidine at all infusion rates. Interestingly, this was associated with an increase in osmolar clearance but not free water clearance. These effects of indomethacin were reversed by infusion of prostaglandin E2. An infusion of prostaglandin E2 attenuated the indomethacin-induced increase in both urine flow rate and sodium excretion, indicating that the effects of indomethacin were mediated by prostaglandin inhibition. These results suggest that endogenous prostaglandin production attenuates the renal effects of clonidine, and as well, that in the presence of α2-adrenoceptor stimulation, prostaglandin E2 mediates an antidiuretic and antinatriuretic effect.Key words: clonidine, indomethacin, prostaglandin E2, diuresis, natriuresis.

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)

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.

The Effect of Papillectomy on Renal Function in the Rat during Hydropenia and after an Acute Saline Load

1972 ◽  
Vol 50 (7) ◽  
pp. 662-673 ◽  
Author(s):  
D. R. Wilson
Keyword(s):  
Renal Function ◽  
Partial Nephrectomy ◽  
Sodium Excretion ◽  
Free Water ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Renal Handling ◽  
Water Excretion ◽  
Fractional Excretion Of Sodium

The effect of unilateral papillectomy on renal function in the rat was compared with the effect of partial nephrectomy which produced a similar decrease in glomerular filtration rate (G.F.R.) in the presence of an intact papilla. Under hydropenic conditions the kidney with papillectomy had a higher urine flow rate, sodium excretion rate, fractional sodium excretion, and osmolar clearance, while urine osmolality was lower. After an acute saline load the differences in sodium and water excretion disappeared, and fractional excretion of sodium and water were significantly higher in both types of kidney damage than in the contralateral control kidney. Free water reabsorption was lower in the papillectomized kidney after saline loading. Thus removal of the papilla resulted in abnormalities in the renal handling of salt and water which varied with the state of hydration of the animal and which were distinct from the effects of a reduction in G.F.R. by partial nephrectomy. It was concluded that the site of nephron loss, whether mainly in the renal medulla or in the cortex, may be another factor, in addition to G.F.R. and tubular reabsorption, which influences sodium and water excretion by the moderately damaged kidney.

Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

2001 ◽  
Vol 281 (2) ◽  
pp. R459-R467 ◽  
Author(s):  
Anders Gabrielsen ◽  
Peter Bie ◽  
Niels Henrik Holstein-Rathlou ◽  
Niels Juel Christensen ◽  
Jørgen Warberg ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Water Immersion ◽  
Free Water ◽  
Ang Ii ◽  
Free Water Clearance ◽  
Fractional Sodium Excretion ◽  
Control Subjects ◽  
Water Clearance

To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 ± 0.03 (mean ± SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits a natriuresis. In HF, WI suppressed ANG II and aldosterone (Aldo) concentrations, increased the release of atrial natriuretic peptide (ANP), and elicited a natriuresis ( P < 0.05 for all) compared with seated control. Compared with control subjects ( n = 9), ANG II, Aldo, and ANP concentrations were increased ( P < 0.05) in HF, whereas absolute and fractional sodium excretion rates were attenuated [47 ± 16 vs. 88 ± 15 μmol/min and 0.42 ± 0.18 vs. 0.68 ± 0.12% (mean ± SE), respectively, both P < 0.05]. When ANG II and Aldo concentrations were further suppressed ( P < 0.05) during WI in HF (by sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased ( P < 0.05) to the level of control subjects (108 ± 34 μmol/min and 0.70 ± 0.23%, respectively). Renal free water clearance increased during WI in control subjects but not in HF, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast, renal free water clearance is attenuated in response to volume expansion in compensated HF despite normalized plasma AVP concentrations.

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.

Response to atrial natriuretic peptide in dogs with hypovolemic acute pancreatitis

1989 ◽  
Vol 256 (2) ◽  
pp. F211-F217
Author(s):  
M. Levy ◽  
P. Cernacek
Keyword(s):  
Blood Pressure ◽  
Acute Pancreatitis ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Plasma Volume ◽  
Sodium Excretion ◽  
Fractional Excretion ◽  
Fractional Excretion Of Sodium ◽  
Acute Renal Insufficiency ◽  
Atrial Natriuretic

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.

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.

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