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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 reduced blood pressure in Cor−/− mice on high salt diet(a) WT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). SBP was measured. (b) Changes in SBP after amiloride treatment were calculated. **p<0.01 vs. WT of the same group by two-way ANOVA. P values in comparisons between groups were indicated. n=4 per group. n.s., not statistically significant.
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Figure 7: Amiloride reduced blood pressure in Cor−/− mice on high salt diet(a) WT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). SBP was measured. (b) Changes in SBP after amiloride treatment were calculated. **p<0.01 vs. WT of the same group by two-way ANOVA. P values in comparisons between groups were indicated. n=4 per group. n.s., not statistically significant.

Mentions: We measured blood pressure in mice treated with amiloride (Figure 7a). No significant changes in blood pressure were observed in Cor−/− mice on the normal salt diet after amiloride treatment. The treatment reduced elevated blood pressure in Cor−/− mice on the high salt diet. In WT mice on the normal or high salt diet, no significant changes in blood pressure were observed after amiloride treatment (Figure 7a). The net effect of amiloride on SBP was significantly greater in Cor−/− mice than that of WT mice on the high salt diet (Figure 7b), indicating that inhibiting ENaC activity increased urinary Na+ excretion and ameliorated hypertension in Cor−/− mice.


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 reduced blood pressure in Cor−/− mice on high salt diet(a) WT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). SBP was measured. (b) Changes in SBP after amiloride treatment were calculated. **p<0.01 vs. WT of the same group by two-way ANOVA. P values in comparisons between groups were indicated. n=4 per group. n.s., not statistically significant.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Amiloride reduced blood pressure in Cor−/− mice on high salt diet(a) WT and Cor−/− mice on 0.3% or 4% NaCl diet were treated with vehicle (−amiloride) or amiloride (3 mg/kg/day, i.p.). SBP was measured. (b) Changes in SBP after amiloride treatment were calculated. **p<0.01 vs. WT of the same group by two-way ANOVA. P values in comparisons between groups were indicated. n=4 per group. n.s., not statistically significant.
Mentions: We measured blood pressure in mice treated with amiloride (Figure 7a). No significant changes in blood pressure were observed in Cor−/− mice on the normal salt diet after amiloride treatment. The treatment reduced elevated blood pressure in Cor−/− mice on the high salt diet. In WT mice on the normal or high salt diet, no significant changes in blood pressure were observed after amiloride treatment (Figure 7a). The net effect of amiloride on SBP was significantly greater in Cor−/− mice than that of WT mice on the high salt diet (Figure 7b), indicating that inhibiting ENaC activity increased urinary Na+ excretion and ameliorated hypertension in Cor−/− mice.

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