scholarly journals Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure

2012 ◽  
Vol 302 (1) ◽  
pp. R166-R174 ◽  
Author(s):  
Bruna H. Inoue ◽  
Leonardo dos Santos ◽  
Thaissa D. Pessoa ◽  
Ednei L. Antonio ◽  
Bruna P. M. Pacheco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Proximal Tubule ◽  
Volume Expansion ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Male Rats ◽  
Sodium Reabsorption ◽  
Mrna Levels ◽  
Transport Activity ◽  
Extracellular Volume Expansion

Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na+/H+ exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.

scholarly journals Left ventricular extracellular volume expansion does not predict recurrence of atrial fibrillation following catheter ablation

2020 ◽  
Vol 43 (2) ◽  
pp. 159-166 ◽  
Author(s):  
Suvai Gunasekaran ◽  
Daniel C. Lee ◽  
Bradley P. Knight ◽  
Jeremy D. Collins ◽  
Lexiaozi Fan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Volume Expansion ◽  
Extracellular Volume ◽  
Left Ventricular ◽  
Extracellular Volume Expansion

Mechanism of natriuresis following intravascular and extracellular volume expansion

1969 ◽  
Vol 47 (2) ◽  
pp. 153-159 ◽  
Author(s):  
H. Sonnenberg ◽  
S. Solomon
Keyword(s):  
Blood Volume ◽  
Volume Expansion ◽  
Filtration Rate ◽  
Extracellular Volume ◽  
Extracellular Fluid ◽  
Sodium Reabsorption ◽  
Fluid Compartment ◽  
Proximal Tubular ◽  
Extracellular Volume Expansion ◽  
A Site

In clearance studies in rats, increases in filtration rate and electrolyte excretion were observed following both intravascular and extracellular fluid volume expansion. The inulin concentration ratio of proximal tubular fluid to plasma was decreased with extracellular expansion. Neither natriuresis nor fractional sodium reabsorption was related to the degree of intravascular expansion. Microperfusion studies demonstrated a decrease in proximal sodium reabsorption only when both intravascular and extravascular volumes were expanded; net sodium transport was not affected by a blood volume increase alone. From the data it is concluded that in the rat an increase in blood volume is followed by a rise of filtration rate and a fall of fractional reabsorption at a site distal to the proximal tubule, resulting in diuresis and natriuresis. If, in addition, the interstitial fluid compartment is expanded, a direct inhibition of the active transport component of proximal Na+ reabsorption occurs.

Interactions between angiotensin and nitric oxide in the renal response to volume expansion

1995 ◽  
Vol 269 (3) ◽  
pp. R504-R510 ◽  
Author(s):  
M. T. Llinas ◽  
J. D. Gonzalez ◽  
F. J. Salazar
Keyword(s):  
Nitric Oxide ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Extracellular Volume ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Synthesis Inhibition ◽  
Renal Response ◽  
Group 2 ◽  
Extracellular Volume Expansion

This study examined, in anesthetized dogs, the possible interactions between nitric oxide (NO) and angiotensin II (ANG II) in mediating the renal response to an extracellular volume expansion (ECVE). It was found that the intrarenal maintenance of ANG II levels (group 1) or the intrarenal NO synthesis inhibition (group 2) did not induce changes in renal hemodynamics but reduced (P < 0.05) the ECVE-induced increments in sodium excretion and fractional lithium excretion (FeLi). In the third group, ANG II synthesis was inhibited during NO synthesis blockade. It was found in this group that the NO synthesis inhibition reduced the ECVE-induced increment in sodium excretion (P < 0.05) but did not modify the ECVE-induced increment in FeLi. These results suggest that the increase of proximal sodium reabsorption induced by the No synthesis inhibition is mediated by endogenous ANG II levels. In the fourth group, it was observed that NO synthesis inhibition, during the intrarenal maintenance of ANG II levels, induced a decrease of renal blood flow (P < 0.05) and reduced the natriuretic response to ECVE to a lower level (P < 0.05) than that observed in groups 1 and 2. The results of this group suggest that endogenous NO modulates the vasoconstrictor and antinatriuretic effects of ANG II during an ECVE. In summary, the results of this study suggest that there is an important interaction between NO and ANG II in mediating the renal response to an ECVE.

scholarly journals Empagliflozin inhibits proximal tubule NHE3 activity, preserves GFR and restores euvolemia in nondiabetic rats with induced heart failure

2020 ◽  
Author(s):  
Flávio A. Borges-Júnior ◽  
Danúbia Silva dos Santos ◽  
Acaris Benetti ◽  
Renato O. Crajoinas ◽  
Ednei L. Antonio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Proximal Tubule ◽  
Extracellular Volume ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Sodium Reabsorption ◽  
Sham Operation ◽  
Lung Weight ◽  
Mortality And Morbidity ◽  
Cardiovascular Outcome Trials

ABSTRACTBackgroundSodium-glucose cotransporter type 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) mortality and morbidity, regardless of the presence or absence of diabetes, but the mechanisms underlying this benefit remain unclear. We tested the hypothesis that the SGLT2 inhibitor empagliflozin inhibits proximal tubule (PT) Na+/H+ exchanger isoform 3 (NHE3) activity and improves renal salt and water handling in nondiabetic rats with HF.Methods and ResultsMale Wistar rats were subjected to myocardial infarction or sham operation. After four weeks, rats that developed HF and sham rats were treated with empagliflozin (EMPA) or untreated for an additional four weeks. EMPA-treated HF rats displayed lower levels of serum brain natriuretic peptide (BNP) and lower right ventricle and lung weight to tibia length than untreated HF rats. Upon saline challenge, the diuretic and natriuretic responses of EMPA-treated HF rats were similar to those of sham rats and were higher than those of untreated HF rats. Additionally, EMPA treatment normalized the glomerular filtration rate and proteinuria in HF rats. PT NHE3 activity was higher in HF rats than in sham rats, whereas treatment with EMPA markedly reduced NHE3 activity. Unexpectedly, SGLT2 function and protein and mRNA abundance were upregulated in the PT of HF rats.ConclusionCollectively, our data show that the prevention of HF progression by empagliflozin is associated with inhibition of PT NHE3 activity and restoration of euvolemia. Moreover, we propose that the dysregulation of PT SGLT2 may be involved in the pathophysiology of nondiabetic HF.SIGNIFICANCE STATEMENTSGLT2 inhibitors represent a class of drugs that were originally developed for improving glycemic control. Cardiovascular outcome trials that were designed to evaluate cardiovascular safety yielded unexpected and unprecedented evidence of the cardiorenal benefits of SGLT2 inhibitor. Many hypotheses have been proposed to explain the mechanisms underlying these effects. Our study demonstrates that SGLT2 inhibition restores extracellular volume homeostasis in nondiabetic heart failure (HF) rats by preserving GFR and inhibiting proximal tubule NHE3-mediated sodium reabsorption. The attenuation of kidney dysfunction may constitute an essential mechanism by which SGLT2 inhibitors attenuate HF development and progression either in the presence or absence of diabetes.

Distal tubular function in superficial rat tubules during volume expansion

1980 ◽  
Vol 239 (3) ◽  
pp. F228-F232 ◽  
Author(s):  
J. Diezi ◽  
M. Nenniger ◽  
G. Giebisch
Keyword(s):  
Sodium Excretion ◽  
Volume Expansion ◽  
Extracellular Volume ◽  
Distal Tubule ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Fluid Delivery ◽  
Distal Tubules ◽  
Extracellular Volume Expansion

Free-flow micropuncture experiments were carried out on superficial late proximal and distal tubules during hydropenic conditions and during extracellular volume expansion. Fluid collected from tubules was analyzed for inulin and sodium. During volume expansion, renal perfusion pressure to one kidney was reduced so that the increase in distal sodium and fluid delivery that normally occurs after saline loading was prevented. Although urinary sodium excretion remained significantly elevated in such kidneys, the rate of sodium reabsorption along the distal tubules was not different from that occurring under nondiuretic conditions. It is concluded that those factors that reduce net sodium transport in the proximal tubule during extracellular volume expansion do not act on superficial distal tubules. Additional factors beyond the distal tubule contribute to increased sodium excretion and can be shown to be activated even when delivery of fluid and sodium out of superficial distal tubules is normal.

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