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Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice.

Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q - Kidney Int. (2012)

Bottom Line: In the knockout mice on the high-salt diet there was an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels.When the knockout mice on the high-salt diet were treated with amiloride, an epithelial sodium channel blocker that inhibits renal sodium reabsorption, the impaired urinary sodium excretion and increased body weight were normalized.Amiloride treatment also reduced high blood pressure caused by the high-salt diet in these mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

ABSTRACT
Corin is a protease that activates atrial natriuretic peptide, a cardiac hormone important in the control of blood pressure and salt-water balance. Here we examined the role of corin in regulating blood pressure and sodium homeostasis upon dietary salt challenge. Radiotelemetry-tracked blood pressure in corin knockout mice on a high-salt diet (4% sodium chloride) was significantly increased; however, there was no such change in similarly treated wild-type mice. In the knockout mice on the high-salt diet there was an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels. When the knockout mice on the high-salt diet were treated with amiloride, an epithelial sodium channel blocker that inhibits renal sodium reabsorption, the impaired urinary sodium excretion and increased body weight were normalized. Amiloride treatment also reduced high blood pressure caused by the high-salt diet in these mice. Thus, the lack of corin in mice impairs their adaptive renal response to high dietary salt, suggesting that corin deficiency may represent an important mechanism underlying salt-sensitive hypertension.

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Amiloride promoted sodium excretion and reduced body weight gain in Cor−/− mice on high salt dietWT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). Changes in urinary sodium excretion in one week (a) and body weight up to 3 weeks (b) were shown. n=5–6 per group. *p<0.05; **p<0.01 by two-way ANOVA; n.s., not statistically significant.
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Figure 6: Amiloride promoted sodium excretion and reduced body weight gain in Cor−/− mice on high salt dietWT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). Changes in urinary sodium excretion in one week (a) and body weight up to 3 weeks (b) were shown. n=5–6 per group. *p<0.05; **p<0.01 by two-way ANOVA; n.s., not statistically significant.

Mentions: Epithelial sodium channel (ENaC) mediates renal Na+ reabsorption, thereby reducing Na+ excretion.27, 28 A recent report showed that the corin/ANP pathway may regulate renal ENaC expression and/or activity.29 To determine if the impaired urinary Na+ excretion in Cor−/− mice on high salt diets was due to an enhanced ENaC activity, we tested the hypothesis that amiloride, an ENaC blocker, might increase urinary Na+ excretion and decrease body weight gain in Cor−/− mice. No significant changes in urinary Na+ excretion were observed in WT and Cor−/− mice on normal salt diet upon amiloride treatment. The treatment, however, corrected impaired Na+ excretion in Cor−/− mice on the high salt diet (Figure 6a). Consistently, Cor−/− mice on the high salt diet and treated with amiloride had body weight gains comparable to that in WT mice (Figure 6b).


Impaired sodium excretion and salt-sensitive hypertension in corin-deficient mice.

Wang W, Shen J, Cui Y, Jiang J, Chen S, Peng J, Wu Q - Kidney Int. (2012)

Amiloride promoted sodium excretion and reduced body weight gain in Cor−/− mice on high salt dietWT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). Changes in urinary sodium excretion in one week (a) and body weight up to 3 weeks (b) were shown. n=5–6 per group. *p<0.05; **p<0.01 by two-way ANOVA; n.s., not statistically significant.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376235&req=5

Figure 6: Amiloride promoted sodium excretion and reduced body weight gain in Cor−/− mice on high salt dietWT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). Changes in urinary sodium excretion in one week (a) and body weight up to 3 weeks (b) were shown. n=5–6 per group. *p<0.05; **p<0.01 by two-way ANOVA; n.s., not statistically significant.
Mentions: Epithelial sodium channel (ENaC) mediates renal Na+ reabsorption, thereby reducing Na+ excretion.27, 28 A recent report showed that the corin/ANP pathway may regulate renal ENaC expression and/or activity.29 To determine if the impaired urinary Na+ excretion in Cor−/− mice on high salt diets was due to an enhanced ENaC activity, we tested the hypothesis that amiloride, an ENaC blocker, might increase urinary Na+ excretion and decrease body weight gain in Cor−/− mice. No significant changes in urinary Na+ excretion were observed in WT and Cor−/− mice on normal salt diet upon amiloride treatment. The treatment, however, corrected impaired Na+ excretion in Cor−/− mice on the high salt diet (Figure 6a). Consistently, Cor−/− mice on the high salt diet and treated with amiloride had body weight gains comparable to that in WT mice (Figure 6b).

Bottom Line: In the knockout mice on the high-salt diet there was an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels.When the knockout mice on the high-salt diet were treated with amiloride, an epithelial sodium channel blocker that inhibits renal sodium reabsorption, the impaired urinary sodium excretion and increased body weight were normalized.Amiloride treatment also reduced high blood pressure caused by the high-salt diet in these mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

ABSTRACT
Corin is a protease that activates atrial natriuretic peptide, a cardiac hormone important in the control of blood pressure and salt-water balance. Here we examined the role of corin in regulating blood pressure and sodium homeostasis upon dietary salt challenge. Radiotelemetry-tracked blood pressure in corin knockout mice on a high-salt diet (4% sodium chloride) was significantly increased; however, there was no such change in similarly treated wild-type mice. In the knockout mice on the high-salt diet there was an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels. When the knockout mice on the high-salt diet were treated with amiloride, an epithelial sodium channel blocker that inhibits renal sodium reabsorption, the impaired urinary sodium excretion and increased body weight were normalized. Amiloride treatment also reduced high blood pressure caused by the high-salt diet in these mice. Thus, the lack of corin in mice impairs their adaptive renal response to high dietary salt, suggesting that corin deficiency may represent an important mechanism underlying salt-sensitive hypertension.

Show MeSH
Related in: MedlinePlus