Increase In Salt Excretion Research Articles

The Role of Epithelial Sodium Channel ENaC and the Apical Cl-/HCO3- Exchanger Pendrin in Compensatory Salt Reabsorption in the Setting of Na-Cl Cotransporter (NCC) Inactivation.

BackgroundThe absence of NCC does not cause significant salt wasting in NCC deficient mice under basal conditions. We hypothesized that ENaC and pendrin play important roles in compensatory salt absorption in the setting of NCC inactivation, and their inhibition and/or downregulation can cause significant salt wasting in NCC KO mice.MethodsWT and NCC KO mice were treated with a daily injection of either amiloride, an inhibitor of ENaC, or acetazolamide (ACTZ), a blocker of salt and bicarbonate reabsorption in the proximal tubule and an inhibitor of carbonic anhydrases in proximal tubule and intercalated cells, or a combination of acetazolamide plus amiloride for defined durations. Animals were subjected to daily balance studies. At the end of treatment, kidneys were harvested and examined. Blood samples were collected for electrolytes and acid base analysis.ResultsAmiloride injection significantly increased the urine output (UO) in NCC KO mice (from 1.3 ml/day before to 2.5 ml/day after amiloride, p<0.03, n = 4) but caused only a slight change in UO in WT mice (p>0.05). The increase in UO in NCC KO mice was associated with a significant increase in sodium excretion (from 0.25 mmol/24 hrs at baseline to 0.35 mmol/24 hrs after amiloride injection, p<0.05, n = 4). Daily treatment with ACTZ for 6 days resulted in >80% reduction of kidney pendrin expression in both WT and NCC KO mice. However, ACTZ treatment noticeably increased urine output and salt excretion only in NCC KO mice (with urine output increasing from a baseline of 1.1 ml/day to 2.3 ml/day and sodium excretion increasing from 0.22 mmole/day before to 0.31 mmole/day after ACTZ) in NCC KO mice; both parameters were significantly higher than in WT mice. Western blot analysis demonstrated significant enhancement in ENaC expression in medulla and cortex of NCC KO and WT mice in response to ACTZ injection for 6 days, and treatment with amiloride in ACTZ-pretreated mice caused a robust increase in salt excretion in both NCC KO and WT mice. Pendrin KO mice did not display a significant increase in urine output or salt excretion after treatment with amiloride or ACTZ.Conclusion1. ENaC plays an important role in salt reabsorption in NCC KO mice. 2. NCC contributes to compensatory salt reabsorption in the setting of carbonic anhydrase inhibition, which is associated with increased delivery of salt from the proximal tubule and the down regulation of pendrin. 3. ENaC is upregulated by ACTZ treatment and its inhibition by amiloride causes significant diuresis in NCC KO and WT mice. Despite being considered mild agents individually, we propose that the combination of acetazolamide and amiloride in the setting of NCC inhibition (i.e., hydrochlorothiazide) will be a powerful diuretic regimen.

Photosynthetic and wood anatomical responses of Tamarixafricana Poiret to water level reduction after short‐term fresh‐ and saline‐water flooding

AbstractIn the Mediterranean basin, Tamarix spp. constitute important populations along rivers and sea coasts, and might be primarily subjected to water level fluctuations and salinization, as a consequence of global climate change. Here, we analyze leaf gas exchange and xylem anatomy during a water level decrease below the soil surface after short‐term flooding with fresh‐ and saline‐water (200 mM) in order to predict Tamarixafricana Poiret responses under future environmental conditions. Fresh‐water level reduction negatively affected stomatal conductance (−56.3 %), but only when water decreased to the lowest level (15 cm below the soil surface). No effects on assimilation rates and xylem vessel dimensions occurred. Under saline conditions, the rate of the water level decrease was lower compared to the non‐saline treatment, as stomatal conductance was negatively affected by salinity (−59.5 %) and significantly declined over time. Moreover, decreases in mean xylem vessel area (−51.3 %), assimilation rates (−52.2 %) and stomatal conductance (−76.0 %) were also observed compared to the control, indicating both an osmotic stress and a toxic effect of NaCl on leaf gas exchange. These leaf responses were probably induced by greater belowground‐root salt absorption and transport compared to previous flooding conditions, as confirmed by the increase in salt excretion (+473.2 %). The results emphasize the survival risk of Tamarix spp. to water level variation under both saline and non‐saline conditions, and the need of management practices focused on the conservation of these populations.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice.

We recently showed that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relation between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of the ANG II type I receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS. Northern blot and immunohistochemical analyses revealed that both drugs caused a drastic stimulation of renin expression in wild-type and VDR-null mice, but renin expression remained much higher in the treated VDR-null mice than in the treated wild-type mice, suggesting that the ANG II feedback mechanism remains intact in the mutant mice. These data firmly established a causative relation between RAS overstimulation and the abnormal volume homeostasis in VDR-null mice and demonstrated that vitamin D repression of renin expression is independent of the ANG II feedback regulation in vivo.

TREATMENT OF HYPERTENSION WITH CHLOROTHIAZIDE

When chlorothiazide is used, lower and, hence, less toxic dosages of other hypertensive agents become effective in controlling blood pressure. Chlorothiazide does not reduce blood pressure in normotensive subjects, although the drug induces the same increase in salt excretion. Regarding the mechanism of antihypertensive effect of chlorothiazide, it may be tentatively concluded that the blood pressure reduction accompanies the salt loss and probably is a consequence of it. When chlorothiazide is added to the regimen of a patient taking ganglionic blocking agents, the dosage of the latter must be reduced by half. The responsiveness of the patient is so remarkably increased by chlorothiazide that, if full dosage is continued, severe hypotension, including postural collapse, usually will occur. The other so-called toxic reactions to chlorothiazide are only extensions of its fundamental saluretic and kaluretic actions. Hypopotassemia is frequent, and potassium supplements should be used when this develops.

Renal function during emotional diuresis

An impressive water, sodium and chloride diuresis is described occurring in a hypertensive subject in response to emotion. Observations were made upon the creatinine, inulin and paraaminohippurate clearances and upon various urinary constituents. An increase in glomerular filtration and a diminished percentage reabsorption of water and salt occurred. It is suggested that the increase in water excretion was due to simultaneous nervous renal vasodilation (with raised glomerular filtration rate) and posterior pituitary inhibition. The increase in salt excretion probably also resulted from the raised glomerular filtration rate, and was accentuated by hypertensive tubular inadequacy.