Faculty Opinions recommendation of In vivo inhibition of renal 11beta-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption.

2001 ◽  
Author(s):  
Jonathan Seckl
Keyword(s):  
Collecting Duct ◽  
Hydroxysteroid Dehydrogenase ◽  
Sodium Reabsorption

RAPID COMMUNICATIONIn vivo inhibition of renal 11β-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption

2001 ◽  
Vol 101 (2) ◽  
pp. 195-198 ◽  
Author(s):  
M. A. BAILEY ◽  
R. J. UNWIN ◽  
D. G. SHIRLEY
Keyword(s):  
Collecting Duct ◽  
Hydroxysteroid Dehydrogenase ◽  
Sodium Reabsorption ◽  
High Dose ◽  
Mineralocorticoid Receptors ◽  
Distal Nephron ◽  
Urinary Recovery ◽  
Distal Tubules ◽  
Adrenalectomized Rats

In order to test the proposal that the aldosterone specificity of mineralocorticoid receptors in the collecting duct depends on inactivation of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD), we have assessed the effect of pharmacological inhibition of 11β-HSD on collecting duct Na+ reabsorption in vivo. Adrenalectomized rats (n = 14) were infused intravenously with high-dose corticosterone, and late-distal tubules were perfused orthogradely with artificial tubular fluid containing [14C]inulin and 22Na; urinary recoveries of the radioisotopes were monitored. Half of the rats received intravenous carbenoxolone to inhibit renal 11β-HSD activity. The urinary recovery of [14C]inulin was complete in both groups of animals (101ŷ2% versus 101ŷ3%), but the recovery of 22Na was lower in carbenoxolone-treated rats (34ŷ5%) than in the corticosterone-alone group (54ŷ4%, P < 0.01). These data, which provide the first demonstration of enhanced Na+ reabsorption in the distal nephron during inhibition of renal 11β-HSD in vivo, strongly support the proposal that 11β-HSD normally prevents endogenous glucocorticoid from exerting mineralocorticoid-like effects.

scholarly journals Collecting Duct Is a Site of Sodium Retention in PAN Nephrosis: A Rationale for Amiloride Therapy

2001 ◽  
Vol 12 (3) ◽  
pp. 598-601 ◽  
Author(s):  
GEORGES DESCHÊNES ◽  
MONIKA WITTNER ◽  
ANTONIO DI STEFANO ◽  
SYLVIE JOUNIER ◽  
ALAIN DOUCET
Keyword(s):  
Collecting Duct ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Puromycin Aminonucleoside ◽  
Aldosterone Receptor ◽  
Collecting Tubules ◽  
A Site

Abstract. Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na+ retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na+ excretion, Na+ balance, or ascites formation in PAN nephrotic rats.

Renal localization and actions of adrenomedullin: a natriuretic peptide

1995 ◽  
Vol 268 (4) ◽  
pp. F657-F663 ◽  
Author(s):  
M. Jougasaki ◽  
C. M. Wei ◽  
L. L. Aarhus ◽  
D. M. Heublein ◽  
S. M. Sandberg ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Sodium Excretion ◽  
Collecting Duct ◽  
Plasma Concentrations ◽  
In Vivo Studies ◽  
Sodium Reabsorption ◽  
Contralateral Kidney ◽  
Arterial Blood ◽  
Group I

Adrenomedullin (ADM) is a newly described 52-amino acid peptide originally isolated from extracts of human pheochromocytoma and, more recently, detected in human plasma. Based on the report that ADM mRNA and immunoreactivity are present in the kidney, the current study was designed to determine the renal distribution of ADM by immunohistochemistry and the renal biological actions of ADM. In the immunohistochemical studies, the present investigation demonstrated the localization of ADM in glomeruli, cortical distal tubules, and medullary collecting duct cells of the normal canine kidney. In the in vivo studies, ADM was administered (0.25 ng.kg-1.min-1 in group I and 1, 5, and 25 ng.kg-1.min-1 in group II) intrarenally in normal mongrel dogs with the contralateral kidney receiving only saline vehicle. Intrarenal infusion of ADM resulted in a marked diuretic and natriuretic response, whereas the contralateral kidney showed no renal effects. These significant natriuresis and diuresis in the ADM kidney were associated with increases in glomerular filtration rate and fractional sodium excretion and with a decrease in distal tubular sodium reabsorption. Intrarenal infusion of ADM also caused an increase in mean arterial blood pressure and a decrease in heart rate. Plasma concentrations of atrial natriuretic peptide, renin activity, aldosterone, and guanosine 3',5'-cyclic monophosphate were not changed during the infusion of ADM. The current study demonstrates that ADM is present in renal glomerular and tubular cells and is a potent natriuretic peptide that may play an important role in the regulation of sodium excretion.

Micropuncture study of the effect of ANP on the papillary collecting duct in the rat

1988 ◽  
Vol 254 (4) ◽  
pp. F477-F483 ◽  
Author(s):  
A. van de Stolpe ◽  
R. L. Jamison
Keyword(s):  
Collecting Duct ◽  
Sodium Concentration ◽  
Sodium Reabsorption ◽  
Micropuncture Study ◽  
Papillary Collecting Duct ◽  
Group 3 ◽  
Group 2 ◽  
Tubule Fluid ◽  
Group 1

Micropuncture collections were obtained from the terminal collecting duct (CD) at base and tip of the renal papilla of the rat. Group 1 was studied before and during infusion with atrial natriuretic peptide (ANP), group 2 was administered the vehicle only, and group 3 received acetazolamide to increase sodium delivery to the base to a similar extent as after ANP. ANP caused a decrease in blood pressure, a slight increase in GFR, natriuresis, and diuresis. Sodium delivery to the collecting duct at the base of the papilla increased. Between base and tip, sodium reabsorption was inhibited. Tubule fluid sodium concentration (TFNa) was increased at the base and remained high at the tip; in contrast TFNa fell between base and tip in control and acetazolamide groups. After acetazolamide, sodium reabsorption in the terminal CD was not inhibited. These results demonstrate that in vivo ANP 1) increases the delivery of sodium to the terminal CD and 2) inhibits sodium reabsorption in the terminal CD. The findings for chloride were similar to those for sodium. ANP also increased delivery of H2O, K, Ca, and Mg to the CD at the papillary base but did not significantly affect their transport by the terminal CD.

Abstract 600: Intrarenal Ghrelin Receptor Antagonism Inhibits cAMP Mediated Angiotensin II Sodium Reabsorption in Normal Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Shetal H Padia
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Ghrelin Receptor ◽  
Sprague Dawley Rats ◽  
Ghrelin Receptors ◽  
Messenger System

An interaction between angiotensin II (Ang II) and ghrelin has been established in many tissues relevant to cardiovascular control, but nothing is known about their relationship within the kidney. Intrarenal ghrelin receptors (GRs) localize to the collecting duct (CD) where they couple to an adenylyl cyclase second messenger system to increase cAMP and ENaC-dependent Na+ reabsorption. Ang II also stimulates the activity of ENaC in the CD (independent of aldosterone), via actions at AT1Rs. The following studies seek to determine whether CD GRs are an important mechanism of Ang II-induced antinatriuresis. Uninephrectomized Sprague-Dawley rats received 3 cumulative 1h renal interstitial (RI) infusions of vehicle 5% dextrose in water (D5W, N=8), Ang II (2 ng/kg/min, N=8), Ang II + D-LYS-GHRP-6, a highly selective GR antagonist (D-LYS, 2, 4, 6 μg/min, N=8) or D-LYS alone (N=8). Urine Na+ excretion rate (UNaV) was measured each hour and compared to baseline, during which only vehicle was infused. RI fluid was collected each hour for cAMP determinations. RI Ang II induced a significant antinatriuresis (UNaV was reduced by 34% at 1h, P<0.01; by 46% at 2h, P<0.001; and by 56% at 3h, P<0.001 from baseline). Ang II-induced antinatriuresis was accompanied by a significant increase in RI cAMP levels from a baseline value of 2.97±0.56 pmol/mL to 10.9±2.2, 13.4±2.2, and 15.3±2.7 pmol/mL after 1h, 2h, and 3h respectively (all P<0.01). However, each of these effects of RI Ang II infusion was abolished by concurrent GR blockade with D-LYS. These data suggest that intact intrarenal GR activity is necessary for Ang II-induced Na+ reabsorption in vivo. Furthermore, since cAMP fails to increase in response to Ang II when GRs are blocked, (and GRs are known to signal via cAMP in the kidney), these data strongly suggest that one of the mechanisms of Ang II-induced Na+ reabsorption in the kidney is via GR-induced increases in cAMP.

Nitric oxide inhibits ADH-stimulated osmotic water permeability in cortical collecting ducts

1996 ◽  
Vol 270 (1) ◽  
pp. F206-F210 ◽  
Author(s):  
N. H. Garcia ◽  
S. I. Pomposiello ◽  
J. L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Water Permeability ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Cortical Collecting Duct ◽  
Urinary Volume ◽  
No Donor ◽  
Osmotic Water ◽  
Spermine Nonoate

Nitric oxide (NO) reduces blood pressure in vivo by two mechanisms, vasodilation and increasing urinary volume: however, the exact mechanism by which it increases urinary volume is not clear. We hypothesized that NO inhibits antidiuretic hormone (ADH)-stimulated fluid reabsorption (J(r)) by the isolated rat cortical collecting duct (CCD) by decreasing water permeability (Pf) and sodium reabsorption (Jna). In the presence of 10(-11) MADH, Jv was 0.15 +/- 0.04 nl.min-1.mm-1; after 10(-6) M spermine nonoate (SPM) was added to the bath. Jv decreased to 0.06 +/- 0.03 nl.min-1.mm-1 (P < 0.03). To investigate whether the inhibition of Jv was the result of decreased Pf and/or Jna, we first tested the effect of SPM on ADH-stimulated Pf. Basal Pf was stimulated to 289.2 +/- 77.3 microns/s after 10(-11) M ADH was added to the bath (P < 0.01). SPM decreased Pf to 159.8 +/- 45.0 microns/s (P < 0.05). To ensure that this effect on Pf was due to NO release, we used another NO donor, nitroglycerin (NTG). Pf was initially -25.8 +/- 18.3 microns/s and increased to 133.9 +/- 30.5 microns/s after addition of 10(-11) M ADH (P < 0.002). NTG, 20 microM, lowered Pf to 92.4 +/- 18.4 microns/s (P < 0.02). In the presence of 10(-9) M ADH, NTG also decreased Pf(P < 0.04). Next we investigated the effect of SPM on ADH-stimulated JNa. In the presence of ADH, JNa was 37.8 +/- 7.3 pmol.min-1.mm-1. After SPM was added, it dropped to 24.3 +/- 5.1 pmol.min-1.mm-1 (P < 0.05). Time controls exhibited no change in ADH-stimulated Jv, Pf, or Jna. We concluded that 1) NO decreases ADH-stimulated water and sodium transport in the isolate CCD, and 2) water reabsorption is inhibited by a primary effect on Pf. A direct effect of NO on the CCD may explain its natriuretic and diuretic effects observed in vivo.

scholarly journals Ghrelin-Induced Sodium Reabsorption Is Mediated by PKA and Microtubule-Dependent αENaC Translocation in Female Rats

2019 ◽  
Vol 3 (11) ◽  
pp. 2088-2106
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
John J Gildea ◽  
Shetal H Padia
Keyword(s):  
Actin Polymerization ◽  
Collecting Duct ◽  
Female Rats ◽  
Sodium Reabsorption ◽  
Na Channel ◽  
Sprague Dawley ◽  
Microtubule Polymerization ◽  
Polymerization Inhibitor ◽  
Underlying Mechanisms

Abstract Intrarenal ghrelin infusion activates ghrelin receptors in the kidney collecting duct (CD) to increase α epithelial sodium (Na+) channel (αENaC)-dependent Na+ reabsorption in vivo, but the underlying mechanisms are unknown. Seventy-two hours following uninephrectomy, 12-week-old female Sprague-Dawley rats received the following renal interstitial (RI) infusions for 1 hour after a 1-hour control: vehicle (n = 10), ghrelin (3 μg/minute; n = 8), ghrelin + phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 (0.1 μg/kg/minute; n = 7), ghrelin + protein kinase A (PKA) inhibitor adenosine 3′5′-cyclic monophosphorothioate, Rp-isomer (10 μg/kg/minute; n = 8), ghrelin + microtubule polymerization inhibitor nocodazole (0.3 μg/kg/minute; n = 7), or ghrelin + actin polymerization inhibitor cytochalasin D (0.3 μg/kg/minute; n = 6). Compared with vehicle infusion, RI ghrelin induced a significant anti-natriuresis (urine Na+ excretion was reduced by 53.7% ± 6.8%; P < 0.001). This effect was abolished during concomitant PKA or microtubule inhibition (106.4% ± 9.4% and 109.7% ± 10.6% of vehicle infusion, respectively; P < 0.01 from ghrelin) but not during concomitant PI3K or actin inhibition (reduced by 48.6% ± 3.9% and 52.8% ± 12.7%, respectively; P < 0.001 and P < 0.01 from vehicle, respectively; P = not significant from ghrelin). Infusions had no effect on mean arterial pressure. Western blot analysis demonstrated that CD membrane but not total αENaC expression increased in response to ghrelin infusion compared with vehicle, (0.39 ± 0.05 vs 0.12 ± 0.02 arbitrary units; P < 0.01). This effect was abolished during PKA or microtubule inhibition but persisted during PI3K or actin inhibition. Neural precursor cell expressed, developmentally down-regulated 4 isoform 2 (Nedd4-2) dependent internalization of αENaC was not affected by ghrelin, indicating that microtubule-dependent forward trafficking of αENaC is necessary for anti-natriuretic responses to ghrelin. Taken together, these studies highlight the importance of PKA and microtubule polymerization in ghrelin-induced αENaC-mediated Na+ reabsorption.

scholarly journals Conditional Transgenic Mice for Studying the Role of the Glucocorticoid Receptor in the Renal Collecting Duct

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2202-2210 ◽  
Author(s):  
Aurélie Nguyen Dinh Cat ◽  
Antoine Ouvrard-Pascaud ◽  
François Tronche ◽  
Maud Clemessy ◽  
Daniel Gonzalez-Nunez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucocorticoid Receptor ◽  
Sodium Channel ◽  
Leucine Zipper ◽  
Collecting Duct ◽  
Extracellular Volume ◽  
Epithelial Sodium Channel ◽  
Sodium Reabsorption ◽  
Renal Collecting Duct

The mineralocorticoid receptor (MR) is a major regulator of renal sodium reabsorption and body fluid homeostasis. However, little is known about glucocorticoid receptor (GR)-dependent renal effects. Glucocorticoids may activate both receptors, so it is difficult to distinguish between MR- and GR-mediated effects in vivo. To overcome this complexity, we used a transgenic mouse model allowing conditional GR overexpression (doxycycline inducible TetON system, Hoxb7 promoter) in the renal collecting duct (CD) to identify GR-regulated genes involved in sodium transport in the CD. In microdissected cortical CD, induction of GR expression led (after 2 d of doxycycline) to increased α-epithelial sodium channel and glucocorticoid-induced leucine zipper and decreased abundance of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase, serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the upstream distal and connecting tubules [distal convoluted tubule (DCT), connecting tubule (CNT)]. Sodium excretion was unaltered, but the urinary aldosterone concentration was reduced, suggesting compensation of transitory extracellular volume expansion that subsequently disappeared. At steady state, i.e. after 15 d of doxycycline administration, transcript abundance remained altered in the CD, whereas mirror changes appeared in the DCT and CNT. Plasma aldosterone or glucocorticoids and blood pressure were all unaffected. These experiments show that: 1) GR, in addition to MR, controls epithelial sodium channel- and glucocorticoid-induced leucine zipper expression in vivo in the CD; 2) with-no-lysine kinase 4 is negatively controlled by GR; and 3) the DCT and CNT compensate for these alterations to maintain normal sodium reabsorption and blood pressure. These results suggest that enhanced GR expression may contribute to enhanced sodium retention in some pathological situations.

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