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.

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.

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.

Effects of α-adrenergic blockade on sodium excretion in normal and chronic salt retaining dogs

1976 ◽  
Vol 54 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Shyan-Yih Chou ◽  
Paul H. Liebman ◽  
Leon F. Ferder ◽  
Daniel L. Levin ◽  
Roy J. Cacciaguida ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Urine Volume ◽  
Vena Cava ◽  
Free Water ◽  
Urinary Sodium Excretion ◽  
Blocking Agent ◽  
Major Effect ◽  
Sodium Reabsorption ◽  
Adrenergic Blockade ◽  
Free Water Clearance

The α-adrenergic blocking agent phenoxybenzamine (PBA) was administered intravenously (10 μg kg−1 min−1) during a steady state water diuresis under pentothal anesthesia to six normal dogs, six dogs with chronic thoracic inferior vena cava constriction and ascites (caval dogs) and seven dogs chronically salt depleted by sodium restriction and furosemide administration. In normal dogs urinary sodium excretion increased significantly from 265 ± 56 (SEM) to 370 ± 65 μequiv./min, whereas no increase in sodium excretion was noted in either caval dogs or salt depleted animals after PBA. In all three groups urine volume, fractional free water clearance and distal sodium load did not change significantly. In normal dogs, distal tubular sodium reabsorption decreased significantly from 73.4 ± 2.8% to 63.1 ± 4.0%, whereas no change was noted in caval or salt depleted dogs. Blood pressure and renal hemodynamics were not significantly altered by PBA administration in any group. These data demonstrate a natriuretic effect of α-adrenergic blockade in normal dogs with the major effect in the water clearing segment of the nephron. The absence of any effect in chronic caval or salt depleted dogs suggests that increased α-adrenergic activity does not play a significant role in the sodium retention of these animals.

The Effect of Indomethacin on Vasopressin-Induced Antidiuresis in Man

1981 ◽  
Vol 61 (4) ◽  
pp. 493-495 ◽  
Author(s):  
P. L. Padfield ◽  
R. J. Grekin
Keyword(s):  
Weight Gain ◽  
Healthy Volunteer ◽  
Creatinine Clearance ◽  
Serum Potassium ◽  
Free Water ◽  
Free Water Clearance ◽  
Renal Response ◽  
Prostaglandin Production ◽  
Endogenous Prostaglandins ◽  
Water Clearance

1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects. 2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance. 3. Although indomethacin reduced maximum free water clearance in five subjects, the antidiuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not. 4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of the response to vasopressin.

A Role for Sodium-Retaining Steroids in the Regulation of Proximal Tubular Sodium Reabsorption in Man

1972 ◽  
Vol 42 (4) ◽  
pp. 423-432 ◽  
Author(s):  
John R. Gill ◽  
Catherine S. Delea ◽  
F. C. Bartter
Keyword(s):  
Flow Rate ◽  
Sodium Excretion ◽  
Free Water ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Urinary Osmolality ◽  
Glomerular Filtrate ◽  
Water Clearance

1. The response to an infusion of 4% (w/v) fructose in water was determined in fifteen women on a daily sodium intake of 100 mEq/day. The results were compared with those obtained during a similar infusion on another day after treatment with deoxycorticosterone (20 mg/day; seven subjects), or spironolactone (200 mg/day; eight subjects), for 1 day before the day of study. 2. Treatment with deoxycorticosterone significantly (P < 0·01) decreased sodium excretion (from a mean value of 391 to 192 μEq/min) and urine flow rate (from 14·3 to 12·4 ml min−1 100 ml−1 of glomerular filtrate) without a change in urinary osmolality or the clearance of inulin. The steroid also increased the fractional reabsorption of sodium at the diluting segment of the nephron, but this increase in reabsorption was not sufficient to compensate for the decrease in delivery of sodium to the site, so that absolute free-water clearance decreased. 3. Treatment with spironolactone significantly (P < 0·01) increased sodium excretion (from 349 to 437 μEq/min) and urine flow rate (from 12·5 to 14·4 ml min−1 100 ml−1 of glomerular filtrate) with essentially no change in urinary osmolality or in inulin clearance. Spironolactone also decreased the fractional reabsorption of sodium at the diluting segment of the nephron, but the degree of inhibition of reabsorption was not sufficient to prevent an increase in free-water clearance as a result of increased delivery of sodium to the site. 4. The findings support the concept that changes in circulating aldosterone can alter the renal excretion of sodium in man by affecting its reabsorption in the proximal tubule as well as in the distal tubule.

Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus

2010 ◽  
Vol 88 (12) ◽  
pp. 1191-1201 ◽  
Author(s):  
S. Mostafa Shid Moosavi ◽  
Masoud Haghani
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Urine Volume ◽  
Free Water ◽  
Urine Flow ◽  
Water Reabsorption ◽  
Free Water Clearance ◽  
Urinary Osmolality ◽  
Antidiuretic Effect ◽  
Water Clearance

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis–diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis–diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

Regulation and function of arginine vasopressin in pregnant sheep

1986 ◽  
Vol 250 (5) ◽  
pp. F777-F780 ◽  
Author(s):  
R. J. Bell ◽  
B. M. Laurence ◽  
P. J. Meehan ◽  
M. Congiu ◽  
B. A. Scoggins ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Infusion Rate ◽  
Plasma Osmolality ◽  
Free Water ◽  
Urinary Flow ◽  
Free Water Clearance ◽  
Pregnant Sheep ◽  
The Mean ◽  
And Function ◽  
Water Clearance

The aim of this study was to investigate the regulation and function of arginine vasopressin (AVP) in pregnant sheep. The mean plasma osmolality of nonpregnant ewes (298 +/- 1.0 mosmol/kg, n = 8) was not significantly different from that of late pregnant ewes (295 +/- 1.1 mosmol/kg, n = 21). The mean resting plasma [AVP] of nonpregnant ewes (4.1 +/- 0.6 pg/ml,n = 8) was not significantly different from that of pregnant ewes (3.3 +/- 0.3 pg/ml,n = 21). In a series of dehydration experiments it was established that the slope of the function relating log [AVP] to plasma osmolality for pregnant ewes (n = 13) was not significantly different from the slope of the function relating log [AVP] to plasma osmolality for nonpregnant ewes (n = 4). When AVP was infused into water-loaded ewes, a significant decrease in urinary flow rate and free water clearance occurred at an infusion rate of 0.003 microgram/h in both the pregnant (n = 4) and nonpregnant (n = 4) animals. Both groups achieved negative free water clearance at an infusion rate of 0.01 microgram/h. These findings suggest that pregnancy does not alter the relationship between plasma osmolality and plasma [AVP] or the renal responsiveness to AVP in sheep.

scholarly journals Evaluation of 24h Urine Volume as an Indicator of Uosm:Posm Ratio and Free Water Clearance in Pregnant Women

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Amy McKenzie ◽  
Colleen Muñoz ◽  
Erica Perrier ◽  
Liliana Jimenez ◽  
Lawrence Armstrong
Keyword(s):  
Pregnant Women ◽  
Urine Volume ◽  
Free Water ◽  
Free Water Clearance ◽  
Water Clearance

THE ACUTE EFFECTS OF INFUSED ADRENAL STEROIDS ON RENAL FUNCTION IN ADRENALECTOMIZED DOGS

1961 ◽  
Vol 37 (2) ◽  
pp. 263-278 ◽  
Author(s):  
J. D. H. Slater ◽  
Paul Mestitz ◽  
Geoffrey Walker ◽  
J. D. N. Nabarro
Keyword(s):  
Urine Volume ◽  
Free Water ◽  
Potassium Excretion ◽  
Adrenal Steroids ◽  
Acute Effects ◽  
Filtration Fraction ◽  
Free Water Clearance ◽  
Sodium And Potassium ◽  
Slow Absorption ◽  
Water Clearance

ABSTRACT Infusions of cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione), prednisolone (11β,17,21-trihydroxy-pregna-1,4-diene-3,20-dione), aldosterone (11β,21-dihydroxy-3,20-dione-pregn-4-en-18-al), and adrenal cortical extract have been given to four adrenalectomized dogs. The changes of inulin, creatinine, para-aminohippuric acid clearances, urine volume, and sodium and potassium excretion have been measured. Between experiments oral replacement therapy was given to obviate the effect of slow absorption of previously injected steroids. The effects of steroid-free control infusions have been studied. Varying the rate of infusion from 1.0–2.6 ml/min, and sodium from 0–170 μeq/min has little effect on glomerular filtration rates (G. F. R.). Infusions of cortisol (1.5 and 10 mg/h), prednisolone (2 mg/h) and adrenal cortical extract (10 ml/h) raised the G. F. R. and lowered the filtration fraction. As the G. F. R. increased the ratio creatinine: inulin clearance fell. The different dogs varied in their responses. Infusions of prednisolone and cortisol (1.5 mg/h) usually increased sodium output as G. F. R. rose. With aldosterone, adrenal cortical extract and cortisol (10 mg/h) there was sodium retention in three of the four dogs, the fourth was resistant to the sodium retaining action of these steroids while the plasma level was high. All steroid infusions increased potassium excretion. Cortisol increased free water clearance independent of G. F. R. provided the infusion rate exceeded 2 ml/min, prednisolone increased both osmolar and free water clearance, aldosterone increased osmolar clearance and reduced free water clearance.

Sign in / Sign up

Export Citation Format

Share Document