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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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Salt-sensitive hypertension in Cor−/− mice(a) Cor−/− and WT mice on a 0.3% NaCl diet (basal) were switched on a 4% NaCl diet for 3 weeks and back to the 0.3% NaCl diet for 3 weeks. Blood pressure was measured by radiotelemetry. Systolic blood pressure (SBP) in Cor−/− and WT mice was shown. n=6 per group. **p<0.01 vs. WT mice of the same group; †p<0.01 vs. Cor−/− mice of basal group by two-way ANOVA. (b) Changes in SBP from the basal group of the same genotype were calculated. n=6 per group. *p<0.05 vs. WT mice of the same group by two-way ANOVA.
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Figure 1: Salt-sensitive hypertension in Cor−/− mice(a) Cor−/− and WT mice on a 0.3% NaCl diet (basal) were switched on a 4% NaCl diet for 3 weeks and back to the 0.3% NaCl diet for 3 weeks. Blood pressure was measured by radiotelemetry. Systolic blood pressure (SBP) in Cor−/− and WT mice was shown. n=6 per group. **p<0.01 vs. WT mice of the same group; †p<0.01 vs. Cor−/− mice of basal group by two-way ANOVA. (b) Changes in SBP from the basal group of the same genotype were calculated. n=6 per group. *p<0.05 vs. WT mice of the same group by two-way ANOVA.

Mentions: We examined the effect of high salt diets on blood pressure in Cor−/− and WT mice. No significant changes were detected when Cor−/− or WT mice were treated with a medium-high (2% NaCl) salt diet for 3 weeks (data not shown). After 1 week on a higher (4% NaCl) salt diet, systolic blood pressure (SBP) increased in Cor−/− mice (from 125.7 ± 3.2 to 133 ± 2.9 mmHg, p<0.01) (Figure 1a). Similar increases in diastolic blood pressure (DBP) and mean arterial blood pressure also were observed (data not shown). In contrast, no significant increase in blood pressure was observed in similarly treated WT mice (Figure 1a). After 3 weeks on 4% NaCl salt diet, Cor−/− mice were switched to a normal salt (0.3% NaCl) diet and their blood pressure remained high for 2 more weeks (Figure 1a). When net changes in SBP were examined, the effect was significantly greater in Cor−/− mice than that in WT controls (Figure 1b), indicating that blood pressure was more sensitive to dietary salt loading in Cor−/− than WT 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)

Salt-sensitive hypertension in Cor−/− mice(a) Cor−/− and WT mice on a 0.3% NaCl diet (basal) were switched on a 4% NaCl diet for 3 weeks and back to the 0.3% NaCl diet for 3 weeks. Blood pressure was measured by radiotelemetry. Systolic blood pressure (SBP) in Cor−/− and WT mice was shown. n=6 per group. **p<0.01 vs. WT mice of the same group; †p<0.01 vs. Cor−/− mice of basal group by two-way ANOVA. (b) Changes in SBP from the basal group of the same genotype were calculated. n=6 per group. *p<0.05 vs. WT mice of the same group by two-way ANOVA.
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Related In: Results  -  Collection

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Figure 1: Salt-sensitive hypertension in Cor−/− mice(a) Cor−/− and WT mice on a 0.3% NaCl diet (basal) were switched on a 4% NaCl diet for 3 weeks and back to the 0.3% NaCl diet for 3 weeks. Blood pressure was measured by radiotelemetry. Systolic blood pressure (SBP) in Cor−/− and WT mice was shown. n=6 per group. **p<0.01 vs. WT mice of the same group; †p<0.01 vs. Cor−/− mice of basal group by two-way ANOVA. (b) Changes in SBP from the basal group of the same genotype were calculated. n=6 per group. *p<0.05 vs. WT mice of the same group by two-way ANOVA.
Mentions: We examined the effect of high salt diets on blood pressure in Cor−/− and WT mice. No significant changes were detected when Cor−/− or WT mice were treated with a medium-high (2% NaCl) salt diet for 3 weeks (data not shown). After 1 week on a higher (4% NaCl) salt diet, systolic blood pressure (SBP) increased in Cor−/− mice (from 125.7 ± 3.2 to 133 ± 2.9 mmHg, p<0.01) (Figure 1a). Similar increases in diastolic blood pressure (DBP) and mean arterial blood pressure also were observed (data not shown). In contrast, no significant increase in blood pressure was observed in similarly treated WT mice (Figure 1a). After 3 weeks on 4% NaCl salt diet, Cor−/− mice were switched to a normal salt (0.3% NaCl) diet and their blood pressure remained high for 2 more weeks (Figure 1a). When net changes in SBP were examined, the effect was significantly greater in Cor−/− mice than that in WT controls (Figure 1b), indicating that blood pressure was more sensitive to dietary salt loading in Cor−/− than WT 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