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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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Losartan did not normalize blood pressure in Cor−/− miceWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or losartan (5, 10 and 20 mg/kg/day, i.p.). SBP was monitored. n=3 per group. *p<0.05 vs. WT of the same group. ‡p<0.05 and †p<0.01 vs. control of the same genotype by two-way ANOVA. Changes in SBP from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n.s., not statistically significant by two-way ANOVA.
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Figure 5: Losartan did not normalize blood pressure in Cor−/− miceWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or losartan (5, 10 and 20 mg/kg/day, i.p.). SBP was monitored. n=3 per group. *p<0.05 vs. WT of the same group. ‡p<0.05 and †p<0.01 vs. control of the same genotype by two-way ANOVA. Changes in SBP from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n.s., not statistically significant by two-way ANOVA.

Mentions: To further examine the potential role of RAAS, we treated Cor−/− mice with losartan, an angiotensin II type 1 receptor blocker. Losartan reduced blood pressure in WT and Cor−/− on both the normal and high salt diets (Figure 5a and c). The extent of reduction was similar in both groups (Figure 5b and d). The treatment did not lower blood pressure in Cor−/− mice to similar levels in WT mice. The results supported that mechanisms other than an enhanced RAAS were likely involved in 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)

Losartan did not normalize blood pressure in Cor−/− miceWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or losartan (5, 10 and 20 mg/kg/day, i.p.). SBP was monitored. n=3 per group. *p<0.05 vs. WT of the same group. ‡p<0.05 and †p<0.01 vs. control of the same genotype by two-way ANOVA. Changes in SBP from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n.s., not statistically significant by two-way ANOVA.
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Related In: Results  -  Collection

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

Figure 5: Losartan did not normalize blood pressure in Cor−/− miceWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or losartan (5, 10 and 20 mg/kg/day, i.p.). SBP was monitored. n=3 per group. *p<0.05 vs. WT of the same group. ‡p<0.05 and †p<0.01 vs. control of the same genotype by two-way ANOVA. Changes in SBP from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n.s., not statistically significant by two-way ANOVA.
Mentions: To further examine the potential role of RAAS, we treated Cor−/− mice with losartan, an angiotensin II type 1 receptor blocker. Losartan reduced blood pressure in WT and Cor−/− on both the normal and high salt diets (Figure 5a and c). The extent of reduction was similar in both groups (Figure 5b and d). The treatment did not lower blood pressure in Cor−/− mice to similar levels in WT mice. The results supported that mechanisms other than an enhanced RAAS were likely involved in 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