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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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Related in: MedlinePlus

Amlodipine normalized blood pressure in Cor−/− mice on 0.3% but not 4% salt dietsWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or amlodipine (0.5 and 1.5 mg/kg/day, i.p.). SBP was measured. *p<0.05; **p<0.01 vs. WT of the same group by two-way ANOVA. Changes in blood pressure from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n=4–5 per group, as indicated. *p<0.05 vs. WT of the same group by two-way ANOVA. n.s., not statistically significant.
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Figure 8: Amlodipine normalized blood pressure in Cor−/− mice on 0.3% but not 4% salt dietsWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or amlodipine (0.5 and 1.5 mg/kg/day, i.p.). SBP was measured. *p<0.05; **p<0.01 vs. WT of the same group by two-way ANOVA. Changes in blood pressure from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n=4–5 per group, as indicated. *p<0.05 vs. WT of the same group by two-way ANOVA. n.s., not statistically significant.

Mentions: To understand the mechanism underlying hypertension in Cor−/− mice on the normal salt diet, we examined the effect of amlodipine, a calcium channel blocker, on blood pressure. Amlodipine reduced blood pressure in Cor−/− and WT mice on the normal salt diet (Figure 8a). The reduction was greater in Cor−/− than WT mice when 1.5 mg/kg of amlodipine was used (Figure 8b). Amlodipine also reduced blood pressure in WT and Cor−/− mice on the high salt diet (Figure 8c). However, the reduction was similar in both groups (Figure 8d). Blood pressure in Cor−/− mice remained significantly higher than that in similarly treated WT mice (Figure 8c).


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)

Amlodipine normalized blood pressure in Cor−/− mice on 0.3% but not 4% salt dietsWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or amlodipine (0.5 and 1.5 mg/kg/day, i.p.). SBP was measured. *p<0.05; **p<0.01 vs. WT of the same group by two-way ANOVA. Changes in blood pressure from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n=4–5 per group, as indicated. *p<0.05 vs. WT of the same group 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 8: Amlodipine normalized blood pressure in Cor−/− mice on 0.3% but not 4% salt dietsWT and Cor−/− mice on 0.3% (a,b) or 4% (c,d) NaCl diet were treated with vehicle (control) or amlodipine (0.5 and 1.5 mg/kg/day, i.p.). SBP was measured. *p<0.05; **p<0.01 vs. WT of the same group by two-way ANOVA. Changes in blood pressure from the control group of the same genotype on 0.3% (b) and 4% (d) NaCl diets were calculated. n=4–5 per group, as indicated. *p<0.05 vs. WT of the same group by two-way ANOVA. n.s., not statistically significant.
Mentions: To understand the mechanism underlying hypertension in Cor−/− mice on the normal salt diet, we examined the effect of amlodipine, a calcium channel blocker, on blood pressure. Amlodipine reduced blood pressure in Cor−/− and WT mice on the normal salt diet (Figure 8a). The reduction was greater in Cor−/− than WT mice when 1.5 mg/kg of amlodipine was used (Figure 8b). Amlodipine also reduced blood pressure in WT and Cor−/− mice on the high salt diet (Figure 8c). However, the reduction was similar in both groups (Figure 8d). Blood pressure in Cor−/− mice remained significantly higher than that in similarly treated WT mice (Figure 8c).

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