Diuretic and natriuretic properties of prestegane B, a mammalian lignan

1987 ◽  
Vol 253 (2) ◽  
pp. R375-R378
Author(s):  
G. E. Plante ◽  
C. Prevost ◽  
A. Chainey ◽  
P. Braquet ◽  
P. Sirois
Keyword(s):  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Urine Flow ◽  
In Vivo Model ◽  
Similar Magnitude ◽  
Site Of Action ◽  
Normal Rat ◽  
Natriuretic Effect

The effect of increasing doses of prestegane B, a synthetic lignan, was examined in the anesthetized normal rat, using clearance methodology. Increasing doses of prestegane B 0.5, 1.0, 2.0, and 5.0 mg) were administered intravenously in our separate groups of hydropenic rats. Urine flow increased by 2.8 +/- 0.3, 4.5 +/- 0.5, 7.7 +/- 0.5, and 18.2 +/- 0.8 microliters/min, respectively, above control values. The rise of urinary sodium secretion was of similar magnitude and averaged 0.4 +/- 0.1, 0.8 +/- 0.2, 1.1 +/- 0.3, and 2.4 +/- 0.3 mu eq/min, respectively. No significant change in urinary phosphate excretion was obtained in all groups of rats, and glomerular filtration rate remained constant from control to experimental clearance periods. The natriuretic effect of prestegane B observed in this in vivo model could be related to the inhibition of the Na+-K+-adenosine triphosphate activity demonstrated in vitro in previous studies from our laboratory. The action of this substance is likely to be situated beyond the proximal tubule, since urinary phosphate was not altered. Prestegane B mimics the effects of other endogenous diuretic and natriuretic hormones, but its site of action and its effect on renal hemodynamics are obviously different.

Atrial extracts increase glomerular filtration rate in vivo

1985 ◽  
Vol 248 (1) ◽  
pp. F24-F30 ◽  
Author(s):  
D. Beasley ◽  
R. L. Malvin
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Recovery Period ◽  
Plasma Renin ◽  
Urine Flow ◽  
Constant Infusion ◽  
Natriuretic Effect

We measured the effect of a constant infusion of rat atrial extract on the glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma renin concentration (PRC) of bioassay rats. The infusion rate of the atrial extract was 0.038 ml/min, which represented 1.25 mg of homogenized atrial tissue/min. To ensure that dead space was cleared, clearance measurements during the atrial extract infusion were not begun until urine flow had increased and 300 microliter of urine had been excreted. In the first series of rats, control GFR was 0.69 +/- 0.05, increased to 1.04 +/- 0.06 during infusion of atrial extract, and then decreased to 0.72 +/- 0.08 ml X min-1 X 100 g-1 during the recovery period. In a second series, RPF was also measured. GFR increased from 0.92 +/- 0.02 to 1.15 +/- 0.05 ml X min-1 X 100 g-1, while RPF was unchanged. In both series, the increase in GFR was statistically significant. Constant infusion of atrial extracts had no significant effect on PRC. These studies provide evidence that an atrial factor can cause a large increase in GFR, which may contribute to the natriuretic effect of atrial extracts.

Endothelin-induced natriuresis and diuresis are pressure-dependent events in the rat

1993 ◽  
Vol 265 (1) ◽  
pp. R90-R96 ◽  
Author(s):  
K. Uzuner ◽  
R. O. Banks
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Arterial Pressure ◽  
Filtration Rate ◽  
Urine Flow ◽  
Female Rats ◽  
Arterial Blood ◽  
Site Of Action ◽  
Baseline Values ◽  
The Right

The goal of the current study was to determine the mechanism by which doses of endothelin (ET) that do not markedly affect the glomerular filtration rate (GFR) cause a natriuresis and diuresis. ET was infused into pentobarbital-anesthetized female rats at 50 ng.kg-1.min-1 iv for 30 min. In controls (n = 6 rats; n = 5 in all other groups), ET increased mean arterial blood pressure (MAP) from 95 +/- 2 to 131 +/- 2 (SE) mmHg, Na excretion (UNa V) from 0.34 +/- 0.07 to 1.83 +/- 0.2 meq/min, and urine flow rate (V) from 13 +/- 1 to 24 +/- 3 ml/min (all P < 0.01 vs. baseline). At 15 min during infusion of ET, the GFR was not affected (2.1 +/- 0.1 to 2.2 +/- 0.1 ml/min) but modestly decreased to 1.8 +/- 0.1 ml/min at 30 min (P < 0.05 vs. baseline). Either removing the capsule from both kidneys during surgery or maintaining renal arterial pressure at baseline values with an adjustable clamp on the aorta above the right renal artery abolished the ET-induced increase in UNa V and V. Meclofenamate also did not alter the ET-induced increase in MAP, V, or UNa V. To determine the intrarenal site of action of ET, experiments were conducted with ET plus amiloride or with a combination of amiloride plus furosemide; there was a larger ET-induced diuresis and natriuresis in amiloride-treated rats and an even larger response with amiloride plus furosemide compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo diuretic actions of renal vasopressin V1 receptor stimulation in rats

1995 ◽  
Vol 268 (3) ◽  
pp. R796-R807 ◽  
Author(s):  
C. Ledderhos ◽  
D. L. Mattson ◽  
M. M. Skelton ◽  
A. W. Cowley
Keyword(s):  
Glomerular Filtration Rate ◽  
Receptor Agonist ◽  
Filtration Rate ◽  
Urine Flow ◽  
Vasopressin Receptor ◽  
Receptor Stimulation ◽  
Water Excretion ◽  
V2 Receptor ◽  
Volume Retention

The specific vasopressin V1 receptor agonist (V1AG; [Phe2,Ile3,Orn8]vasopressin) was infused (2.0 ng.kg-1.min-1) into the renal medullary interstitial space to determine the effects of selective medullary V1 receptor stimulation on sodium and water excretion in normal rats. Responses were compared with those of arginine vasopressin (AVP) and vasopressin V2 receptor stimulation resulting from infusion of a V1 receptor antagonist with AVP. Medullary infusion of V1AG or AVP in euvolemic rats produced no changes in hemodynamics or glomerular filtration rate. V1AG increased urine flow > 60% in euvolemic rats, whereas no change was observed with AVP. This response could not be explained by a rise of arterial pressure or by volume retention. With V2 stimulation in euvolemic rats, urine flow was decreased. In water diuretic rats, V1AG produced no change, whereas AVP infusion decreased urine flow. The results provide in vivo evidence that tubular V1 vasopressin receptor activity results in increased urine flow and thereby modulates the antidiuretic actions of vasopressin in the euvolemic state.

Renal Na+-K+-ATPase in renin release

1982 ◽  
Vol 243 (6) ◽  
pp. F598-F603
Author(s):  
M. A. Cruz-Soto ◽  
J. E. Benabe ◽  
J. M. Lopez-Novoa ◽  
M. Martinez-Maldonado
Keyword(s):  
Sodium Excretion ◽  
Filtration Rate ◽  
Urine Flow ◽  
Renin Secretion ◽  
Juxtaglomerular Cells ◽  
Secretory Rate ◽  
Level Of Activity ◽  
Anesthetized Dogs ◽  
Natriuretic Effect

The effects of ouabain and furosemide on renin secretion, renal function, and renal Na+-K+-ATPase were investigated in anesthetized dogs. Furosemide (2 mg/kg) induced significant diuresis, natriuresis, an increase in renal blood flow (RBF), and a fivefold increase in renin secretory rate (RSR), but no changes in glomerular filtration rate (GFR). Infusion of ouabain (1 microgram . kg-1 . min-1) into one renal artery during furosemide diuresis increased fractional sodium excretion from 22 +/- 2 to 30 +/- 3% from the ipsilateral kidney but did not change urine flow, RBF, or GFR, whereas RSR fell to control values (698 +/- 203 to 137 +/- 43). When ouabain preceded furosemide, the rise in RBF and RSR induced by furosemide was abolished but sodium excretion increased. Ouabain infused in vivo inhibited Na+-K+-ATPase in microsomal fractions from cortex (34%) and medulla (27%) as compared with control. Neither saline nor furosemide exerted any effect on Na+-K+-ATPase. Moreover, the effect of ouabain alone on Na+-K+-ATPase was not different from that of ouabain plus furosemide. No changes in Mg2+-ATPase were detected in any of the experiments. These results indicate that inhibition of renal Na+-K+-ATPase abolishes furosemide-induced renin secretion despite potentiation of the natriuretic effect of the diuretic. It is apparent that the level of activity of Na+-K+-ATPase is of prime importance for renin secretion. In addition, ouabain may act directly on the juxtaglomerular cells to inhibit renin secretion.

Diluting power of thick limbs of Henle. III. Modulation of in vitro diluting power

1988 ◽  
Vol 255 (6) ◽  
pp. F1145-F1154 ◽  
Author(s):  
W. B. Reeves ◽  
D. A. Molony ◽  
T. E. Andreoli
Keyword(s):  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Osmotic Gradient ◽  
Salt Balance ◽  
Perfusion Rate ◽  
Passive Permeability ◽  
Single Nephron ◽  
Static Head

This paper considers the quantitative interplay of various factors in modulating diluting power of in vitro medullary and cortical thick ascending limbs of Henle (MTAL and CTAL, respectively) segments from mouse and rabbit. Experimentally, the measured diluting power of the in vitro rabbit CTAL is greater than that of the rabbit MTAL, although the inherent rate of net Cl- absorption at high perfusion rates is considerably greater in the rabbit MTAL than in the rabbit CTAL. Similar results apply when comparing the rabbit CTAL to the mouse MTAL exposed to antidiuretic hormone (ADH). Our calculations show that, in the rabbit CTAL, the measured static head luminal salt concentration can be accounted for quantitatively by the measured rate of net salt absorption at a high perfusion rate together with the passive permeability coefficients for Na+ and Cl-. Moreover, with perfusion rates of 10% of single-nephron glomerular filtration rate, the transport properties of the CTAL predict that, at the end of the CTAL, the static head luminal Cl- concentration occurs if the initial perfusate contains either 50 or 150 mM Cl-. Thus one can argue that, in vivo the CTAL may be the cardinal determinant of the TAL contribution to diluting power and to external salt balance. The relatively blunted diluting power of in vitro MTAL segments can be accounted for quantitatively by assuming that luminal dilution, and the attendant osmotic gradient from lumen to cell, suppresses the inherent rate of transcellular Cl- transport. Our calculations also show that prostaglandin E2 and peritubular osmolality increases blunt tubular diluting power. Thus in vivo, the MTAL segment may be the cardinal determinant of TAL contribution to concentrating power and to intrarenal salt balance.

scholarly journals Adipokines as a link between obesity and chronic kidney disease

2013 ◽  
Vol 305 (12) ◽  
pp. F1629-F1636 ◽  
Author(s):  
Jessica F. Briffa ◽  
Andrew J. McAinch ◽  
Philip Poronnik ◽  
Deanne H. Hryciw
Keyword(s):  
Chronic Kidney Disease ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Cell Types ◽  
Peripheral Tissues ◽  
Increased Risk

Adipocytes secrete a number of bioactive adipokines that activate a variety of cell signaling pathways in central and peripheral tissues. Obesity is associated with the altered production of many adipokines and is linked to a number of pathologies. As an increase in body weight is directly associated with an increased risk for developing chronic kidney disease (CKD), there is significant interest in the link between obesity and renal dysfunction. Altered levels of the adipokines leptin, adiponectin, resistin, and visfatin can decrease the glomerular filtration rate and increase albuminuria, which are pathophysiological changes typical of CKD. Specifically, exposure of the glomerulus to altered adipokine levels can increase its permeability, fuse the podocytes, and cause mesangial cell hypertrophy, all of which alter the glomerular filtration rate. In addition, the adipokines leptin and adiponectin can act on tubular networks. Thus, adipokines can act on multiple cell types in the development of renal pathophysiology. Importantly, most studies have been performed using in vitro models, with future studies in vivo required to further elucidate the specific roles that adipokines play in the development and progression of CKD.

Role for Endothelin in the Renal Responses to Radiocontrast Media in the Rat

1994 ◽  
Vol 87 (4) ◽  
pp. 427-434 ◽  
Author(s):  
S. Oldroyd ◽  
S.-J. Slee ◽  
J. Haylor ◽  
S. K. Morcos ◽  
C. Wilson
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Initial Increase ◽  
Radiocontrast Media ◽  
Perfusate Flow ◽  
Renal Responses ◽  
Anaesthetized Rat

1. The involvement of endothelin in the renal responses to radiocontrast media was examined in the rat in vitro and in vivo using BQ123, a selective endothelin (ETA) receptor antagonist, and phosphoramidon, an endothelin-converting enzyme inhibitor. 2. For experiments in vitro, an isolated perfused rat kidney was employed perfusing in closed circuit with an albumin-based Krebs-Henseleit solution. The effects of BQ123 and phosphoramidon on the renal responses to iotrolan (iso-osmolar radiocontrast media) and diatrizoate (high-osmolar radiocontrast media) were examined. In vivo, renal conductance was measured using a Doppler flow probe in the anaesthetized rat pretreated with indomethacin, and the effects of BQ123 and phosphoramidon on the renal response to intravenous diatrizoate were examined. 3. In vitro, iotrolan and diatrizoate both produced a biphasic effect on the glomerular filtration rate, characterized by a transient increase followed by a sustained fall. Pretreatment with BQ123 (10 μmol/l), but not phosphoramidon (1 mmol/l), prevented both the increase and the sustained fall in glomerular filtration rate induced by radiocontrast media. 4. In vitro, iotrolan and diatrizoate both produced a sustained fall in renal perfusate flow. An initial increase in renal perfusate flow was only observed with diatrizoate. Pretreatment with BQ123 (10 μmol/l), but not with phosphoramidon (1 mmol/l), markedly inhibited the sustained fall in renal perfusate flow produced by both iotrolan and diatrizoate. BQ123 (10 μmol/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate. 5. In vivo, in the anaesthetized rat treated with indomethacin, the sustained fall in renal conductance produced by diatrizoate (2.9 g of iodine/kg, intravenously) was markedly inhibited by pretreatment with BQ123 (1 mg/kg) but not with phosphoramidon (10 mg/kg). 6. A role for endothelin as a mediator of the renal responses of radiocontrast media is proposed.

scholarly journals Endothelin induces diuresis and natriuresis in the rat by acting on proximal tubular cells through a mechanism mediated by lipoxygenase products.

1991 ◽  
Vol 2 (1) ◽  
pp. 57-69
Author(s):  
N Perico ◽  
R P Cornejo ◽  
A Benigni ◽  
B Malanchini ◽  
J R Ladny ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Atrial Natriuretic Peptide ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Lipoxygenase Products ◽  
Natriuretic Effect

Besides being a potent renal vasoconstrictor, endothelin causes diuresis and natriuresis. At which site along the nephron and how endothelin alters water and sodium handling in the tubule remain to be clarified. It was found that endothelin (75 pmol) given as an i.v. infusion in vivo to rats caused diuresis and urinary sodium excretion to double but did not affect glomerular filtration rate and renal plasma flow. On raising the dose of endothelin to 150 pmol, a further increase in diuresis and natriuresis was found, whereas glomerular filtration rate fell 33% and renal plasma flow fell 36%; 300 pmol of endothelin reduced glomerular filtration rate by 73% and renal plasma flow by 77% but did not significantly affect diuresis and absolute sodium excretion. It did, however, increase fractional sodium excretion eightfold. Lithium clearance studies of changes in tubular handling of water and sodium indicated that infusion of 150 pmol of endothelin to rats caused a reduction in absolute (pre, 84.7 +/- 5.9; post, 47.9 +/- 6.1 microEq/min/100 g) and fractional (pre, 85.7 +/- 3.0; post, 64.7 +/- 6.4%) proximal reabsorption of sodium. Endothelin infusion (150 pmol) was not associated with any significant change in plasma atrial natriuretic peptide levels, which on average remained comparable to those in rats given the vehicle alone (49.7 +/- 8.4 versus 46.3 +/- 5.6 pg/mL). In the isolated perfused rat kidney preparation, exposure to 150 pmol of endothelin significantly increased fractional sodium excretion over preinjection values (pre, 2.2 +/- 0.2; post, 7.3 +/- 1.0%) despite a marked decrease in glomerular filtration rate and renal perfusate flow. Additional in vivo experiments showed that oral administration of the specific 5-lipoxygenase inhibitor L-651,392 to rats prevented the increase in urine flow rate (pre, 5.7 +/- 0.1; post, 6.6 +/- 0.8 microL/min), and in absolute (pre, 0.33 +/- 0.04; post, 0.37 +/- 0.05 microEq/min) and fractional (pre, 0.10 +/- 0.02; post, 0.11 +/- 0.03%) sodium excretion caused by bolus i.v. infusion of endothelin (150 pmol). Similarly, a specific leukotriene C4/D4 receptor antagonist, L-649,923, also prevented the diuretic and natriuretic effect of 150 pmol of endothelin i.v. infusion. These findings show that (1) endothelin has a diuretic and natriuretic effect that is independent of its action on renal hemodynamics; (2) this effect depends on a direct action on the proximal tubules; (3) atrial natriuretic peptide does not appear to be involved in this effect; and (4) the diuretic and natriuretic responses to endothelin are mediated by 5-lipoxygenase products.

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